Chicken embryo lethal orphan (CELO) virus

ABSTRACT

A CELO virus obtained by in vitro manipulation of a plasmid-cloned CELO virus DNA is suitable for the production of vectors for gene therapy and as a vaccine against infectious diseases in humans and animals, particularly birds.

The invention relates to adenoviruses. The large family of adenovirusesis subdivided according to its host into adenoviruses which infectmammals (the mastadenoviridae) and adenoviruses which infect birds (theaviadenoviridae). The CELO virus (Chicken Embryo Lethal Orphan; articleby Mcferran, et al., 1977; McCracken and Adair, 1993) was identified asan infectious agent in 1957 (Yates and Fry, 1957). CELO virus isclassified as a poultry adenovirus type 1 (FAV-1) and first arousedinterest because of its property of being tumorigenic in baby hamsters.However, since infection with the CELO virus does not have any serioushealth and economic consequences, the interest in this virus disappearedin recent years. The FAV-1 adenoviruses can be isolated from healthychickens and do not cause any disease when reintroduced experimentallyinto chickens (Cowen, et al., 1978). Their isolation from sick birds ispresumably the result of adenovirus replication in a host which has animmune system weakened by other influences.

The general structural organisation of CELO virus, with an icosahedralcapsid of 70-80 nm, made up of hexon and penton structures, is similarto that of the mammalian adenoviruses (Laver, et al., 1971). The CELOvirus genome is a linear, double-stranded DNA molecule, the DNA beingcondensed inside the virion by virus-coded core proteins (Laver et al.,1971; Li, et al., 1984b). The CELO virus genome has covalently boundterminal proteins (Li, et al., 1983) and the genome has invertedterminal repeats (ITRs), although they are shorter than the mammalianITRs (Aleström, et al., 1982b; Sheppard and Trist, 1992). The CELO viruscodes a protease with 61-69% homology for the mammalian adenovirusproteases (Cai and Weber, 1993).

There are significant differences between CELO virus and themastadenoviruses. CELO virus has a larger genome, with sequence homologywith Ad5 which can only be detected in two short regions of the CELOvirus genome (by hybridisation) (Aleström, et al., 1982a). The CELOvirion has been reported to have two fibres of different lengths at eachvertex. The CELO virus cannot complement the E1A functions of Ad5, andthe replication of CELO virus is not made easier by the activity ofAd5E1 (Li, et al., 1984c).

Within the scope of the present invention, total sequence analysis ofthe CELO virus was carried out; on the one hand because it is useful forunderstanding the biology of adenoviruses to clarify the genomicorganisation of an adenovirus which is very remote from the mammalianadenoviruses generally studied. Since the conditions for transmissionand survival for a virus which infects a type of bird are presumablydifferent than for mammalian viruses, it is possible that the birdadenoviruses have acquired new virus functions or exhibit a higherdegree of variability than the mastadenoviridae. The complete CELO virussequence also permits changes in the CELO virus genome with respect tofunctional analysis.

Since adenovirus vectors have proved highly effective vectors for genetransfer (see the summarising article by Graham, 1990; Kozarsky andWilson, 1993; Trapnell and Gorziglia, 1994), the complete CELO virussequence, on the other hands is particularly interesting as the basisfor preparing new recombinant vectors for gene transfer.

Sequence analysis has shown that the CELO virus genome has 43.8 kb,being more than 8 kb longer than the human subtypes Ad2 and Ad5. Thegenes for the main structural proteins (hexon, penton based, IIIa,fibres, pVI, pVII, pVIII) are on the one hand both present and alsolocated at the corresponding sites in the genome. The genes of the earlyregion 2 (E2; DNA binding protein, DNA polymerase and terminal protein)are also present. However, the CELO virus lacks sequences homologous tothe regions E1, E3 and E4 of the mammalian adenoviruses. There areapproximately 5 kb at the left hand end and 15 kb at the right hand endof the CELO virus genome, where there is only restricted homology or nohomology at all with the mastadenovirus genomes. These new sequencescontain a number of open reading frames, and it can be assumed thatthese code for functions which replace the missing E1, E3 and possiblyE4 regions.

Parts of the CELO virus sequence have already been published; they arelisted in Table 1, as are the differences between the sequence knownfrom the databank and the sequence determined within the scope of thepresent invention. From studies concentrating on specific viral genes, ahomolog of the VA RNA gene of mastadenovirus was known (Larsson, et al.,1986) and part of the genome sequence which carries the endoprotease hasbeen described (Cai and Weber, 1993). In addition, fragments of the CELOvirus genome have been published (Akopian, et al., 1990; Akopian, etal., 1992; Hess, et al., 1995). The sequence of the penton base of therelated virus FAV-10 has also been reported (Sheppard and Trist, 1992).Some other sequence fragments have been deposited in the databank andare also shown in Table 1. In all, about 50% of the CELO virus genome isavailable in the form of fragments (total about 24 kb). The sequenceobtained within the scope of the present invention is complete and hasthe advantage of having been obtained from a single isolated material.

The total sequence of the CELO virus is shown in the sequence listing(in the sequence listing the word “complementary” indicates that theopen reading frames are present in the reverse arrangement). It shows alarge number of striking differences between Ad2 and the CELO virus. Theorganisation of the recognisable open reading frames (ORFs) of the CELOvirus genome based on the sequence analysis, compared with Ad2, is shownin FIG. 1A: the Figure shows an overview of the genomic organisation ofAd2/5 and CELO virus. The arrows indicate the position of the codingregions but not the exact cleavage patterns of the gene products. Thepattern of the CELO virus also (in the first 6,000 bp and in the last13,000 bp) gives all the non-associated open reading frames which beginwith a methionine and which code for more than 99 amino acid groups. Thecentral region of the two genomes which show homology on the basis ofdot matrix analysis (cf. FIG. 3) and the regions at the ends of the CELOvirus genome which have no homology with other adenoviruses (“unique toCELO”) are given. The abbreviations in the Figure, which also correspondto those in the Tables, have the following meanings: PB, penton base;EP, endoproteinase; DBP, DNA binding protein; bTP, preterminal protein;pol, DNA polymerase.

The sequenced CELO virus genome has a length of 43,804 bp and has acontent of G+C of 54.3%. It had already been presumed at an earlierstage that the CELO virus genome is much larger than the mastadenovirusgenome with 34-36 kb; it has been found that the CELO virus DNA has aweight of 30×10⁶ Daltons, determined according to its sedimentationcoefficient (Laver, et al., 1971), compared with 24×10⁶ Daltons for Ad2(Green, et al., 1967). The size of the CELO virus genome determined bythe addition of the restriction fragments is about 43 kb (Cai and Weber,1993; Denisova, et al., 1979). A Pulsed Field Gel Analysis of the CELOvirus genome isolated from purified virions is shown in FIG. 2A and iscompared with the DNA isolated from Ad5 dl1014 (34,600 bp; Bridge andKetner, 1989) or Wild-type Ad5-virions (35,935 bp; vt300; Chroboczek, etal., 1992; Jones and Shenk, 1978); a mixture of uncleaved bacteriophageλ-DNA and γ-DNA cleaved with five different restriction enzymes (Biorad)was used as the size marker (tracks 1 and 7 show the molecular weightmarkers, track 2 shows the DNA of Ad5 dl1014, track 3 shows the DNA ofAd5 wt300, track 4 shows the CELO virus DNA, track 5 shows the DNA ofOTE, track 6 shows the DNA of Indiana C). FIG. 2A shows that the CELOvirus genome has a length of 44 kb. From this analysis it is clear thatthe CELO virus genome is actually substantially larger than the genomeof the mammalian virus. Calculations based on the migration of fragmentsof the lambda bacteriophage give a size of 43 kb for the CELO virusgenome. The DNA extracted from two other FAV-1 isolates, Indiana C andOTE, co-migrates with the CELO virus species, which is further evidenceof the size of the CELO virus genome. FIG. 2B shows that the CELO virussequence contained in the bacterial plasmid pBR327 has the same size.

There is no identifiable E1 region. No significant homology could befound between the CELO virus genome and the first 4,000 bp of Ad2. Thereare a few small open reading frames in the first 5,000 bp of CELO viruswhich might possibly perform some of the E1 tasks. An open reading frameat the right hand end of the virus genome (GAM-1) may replace E1B 19K infunctional assays without there being any significant homology betweenGAM-1 and E1B 19K. In order to confirm that the left hand end originatesfrom the Wild type CELO virus genome and is not the sequence of a clonedvariant, various tests were carried out; comparison of the directsequence analysis of CELO virions at three different sites with thecorresponding sites of the cloned sequences; Southern analyses with DNAfrom various virus isolates which yielded the same restrictionfragments; pulsed field gel electrophoresis of various virus genomeswhich showed no heterogenicity.

There is no identifiable E3 region; the two small open reading frames inthe corresponding region of the CELO virus have no significant homologywith the E3 functions described.

There is a group of small open reading frames between 36,000 and 31,000the position of which indicates the mammalian virus E4 region, but withadditional 8 kb sequence at the right hand end of the CELO virus.

Nor was any sequence resembling protein IX identified (protein IX isessential for the hexon-hexon interactions and the stability of themammalian adenovirus virions).

A protein V gene was not identified either.

The following regions are conserved between CELO virus and Ad2: thecentral part of the CELO virus genome, from the IVa2 gene (approximatelyfrom nucleotide (nt) 5,000) on the left hand strand up to the fibregenes on the right hand strand (approximately up to nt 33,000) isorganised as in the mastadenoviruses, and the majority of the importantviral genes can be identified both by their position and by sequencehomology. Earlier studies on the homology between CELO and Ad2(Aleström, et al., 1982a) showed two regions of the CELO virus whichcross-hybridise with the Ad2 sequence. These two fragments are nt 5,626to 8,877 (coding for IVa2 and the carboxy terminus of DNA polymerase)and nt 17,881 to 21,607 (coding for the hexon). The dot matrix analysisshown in FIG. 3 (carried out using the UWGCG program Compare with awindow of 30 and a stringency of 20; summarised in FIG. 1A) shows thatthe total DNA sequence homology between CELO virus and Ad5 is mapped inthe central region of the CELO virus genome. This is to be expectedbecause the capsid proteins are coded in this central region and thecoarse structure of the CELO virion is comparable with the capsid of themammalian adenovirus (Laver, et al., 1971; Li, et al., 1984a). The geneswhich code for proteins corresponding to the human adenovirus proteinshexon, IIIa, penton base, protein VI and protein VIII, are present, andindeed in the expected sequence and position (FIG. 1A and Table 2A;Table 2B shows non-associated open reading frames which code for geneproducts with more than 99 amino acid groups). Each vertex of themastadenovirus virion contains a pentamer of the penton base protein inconjunction with a single fibre consisting of three copies of the fibrepolypeptide. Ad2, like most mastadenoviruses, has a single fibre gene,some adenovirus types have two fibre genes. The CELO virus genome codesfor two fibre polypeptides of different lengths and sequences.

DNA binding proteins were identified in the region E2 (Li, et al.,1984c); four proteins with similar peptide maps were described,indicating a single precursor which is then cleaved or decomposed. Theleft hand open reading frame of the CELO virus genome, starting at nt23,224, is located in the expected DNA binding protein region. The genescoding for DNA polymerase and pTP (pre-terminal protein) are present andin the expected positions (FIG. 1A, Table 2A).

With a view to the preparation of vectors based on the CELO virus it isuseful to identify the mechanisms which the CELO virus uses in order topackage almost 44 kb of DNA into a virion which is of a similar size tothe human adenoviruses which are subjected to considerable restrictionson their packaging capacity (Bett, et al., 1993; Caravokyri and Leppard,1995; Ghosh-Choudhury, 1987). One possibility is that the CELO virion,although virtually identical in size to Ad2 and Ad5, has a sufficientlywidened structure in order to accommodate the larger genome. Analternative hypothesis is that CELO has a different mechanism forcondensing DNA and therefore has differences in its provision of coreproteins which are responsible for DNA packaging. Laver et al., in 1971identified two proteins in the nucleus of the CELO virus and noted theabsence of a molecule resembling protein V. Li, et al., 1984b, usedelectrophoresis with a higher resolution and reported a nuclearstructure with three polypeptides (20 kD, 12 kD and 9.5 kD). These twofindings lead one to conclude that the CELO virus must lack the largerbasic nuclear protein V (41 kD) which occurs in mammalian adenoviruses.Perhaps the absence of protein V and/or the presence of smaller basicproteins is responsible for the additional packaging capacity of theCELO virion. The smallest of the CELO virus core proteins identified byLi, et al., 1984b (9.5 kD) is most closely associated with the virusDNA, similar to protein VII of the human adenovirus. An open readingframe which leads one to expect a protein with 8,597 D having 72 aminoacids is located at nt 16,679; the coded protein is rich in arginine(32.9 mol %) and contains two cleavage sites for protease (pVII of Ad2has only one cleavage site). An open reading frame which leads one toexpect a protein with 19,777 D having 188 amino acid groups is locatedat nt 16,929. The protein has protease cleavage sites after groups 22,128 and 145, and the carboxy-terminal groups have homology with pX ofmastadenovirus. FIG. 4 shows the amino acid sequences of protein VII andpX of various mastadenoviruses compared with the CELO virus and the coreproteins Core 2 and Core 1 of FAV-10. The sequences were arranged usingthe UWGCG Bestfit Program with a gap weight of 3.0 and a weight and gaplength (“Gap Length Weight”) of 0.1. The protease cleavage sites ofadenovirus are underlined. In connection with this it is interestingthat the mastadenovirus DNA binding protein designated “mu” consistingof 19 groups is formed by two protease cleavings of the pX precursor(Hosokava and Sung, 1976; Weber and Anderson, 1988; Anderson, et al.,1989). Cleaving of the protein having 188 groups after groups 128 and145 would produce a mu-like basic protein consisting of 17 groups (41%arginine, 12% lysine). The uncleaved form of the protein is also highlybasic; the uncleaved copies of this protein could correspond to the 20kD core protein observed by Li, et al., 1984b; a third 12 kD coreprotein identified by these authors could not yet be assigned.

Moreover, some new or non-assigned open reading frames were found in theCELO virus genome. A summary of these open reading frames is shown inTable 2A; these open reading frames are also given in FIG. 1A. Thissummary was restricted to the sequences from nt 0-6,000 and31,000-43,804 and only ORFs which contain a methionine group and codefor a protein >99 amino acid groups are mentioned. As already stated,there is an ORF at nt 1999 which codes for a protein having homologywith parvovirus-REP, and an ORF at nt 794 having homology with dUTPaseand Ad2 E4 ORF1. The objective of the present invention was to prepare anew CELO virus.

Thus, on the basis of the complete CELO virus genome sequence, thepresent invention relates to a CELO virus obtained by in vitromanipulation of a plasmid-cloned CELO virus DNA.

The CELO virus according to the invention derived from the genomic DNAcontains, in a preferred embodiment, the left and right terminal repeatand the packaging signal and has modifications in the form of insertionsand/or deletions and/or mutations in regions of the CELO virus DNA whichare different therefrom.

The left or right terminal repeat (“Inverted Terminal Repeat”, ITR)extends from nucleotides 1-68 or from nucleotides 43734-43804, thepackaging signal (also referred to as “Psi”) extends from nucleotides70-200. Modifications in DNA sections other than these ensures that thegenes affected by the modification are non-functional or are deleted.

Preferably, modifications of the CELO virus genome are undertaken whichare located on a section of the CELO virus DNA which includes thenucleotides from about 201 to about 5,000 (following the left terminalrepeat of the section at the left hand end, hereinafter referred to as“Section A”) and/or on a section which includes the nucleotides fromabout 31,800- about 43,734 (the section at the right hand end located infront of the right terminal repeat, hereinafter referred to as “SectionB”) and/or on a section which includes the nucleotides from about28,114-30,495 (the region of the fibre 1 gene, hereinafter referred toas “Section C”).

A CELO virus in which certain genes are non-functional or are deleted,e.g. genes which affect the immune response of the host, such asantagonists to genes of the E3 region of mammalian adenoviruses, can beused as a vaccine.

In one embodiment of the invention the CELO virus contains one or moreforeign DNA molecules, particularly a foreign DNA which is to beexpressed in a host organism. In this embodiment the CELO virus acts asa vector which is capable of transporting the foreign DNA into highereukaryotic cells, tissue or organisms, particularly mammals and birds,and expressing it therein.

Suitable insertion sites for the foreign DNA are the sections A and/or Band/or C.

The foreign DNA preferably replaces one or more sequences from thesesections.

The CELO virus according to the invention is contained on a plasmidwhich is replicatable in bacteria or yeast and which yields virusparticles after being introduced into suitable cells. Examples ofsuitable cells are bird embryo kidney or liver cells.

With a view to using a recombinant CELO virus vector for gene therapy,the foreign DNA may consist of one or more therapeutically active genes.Examples of these are genes coding for immunomodulators or modulators ofinflammatory processes (cytokines such as IL-2, GM-CSF, IL-1, IL-6,IL-12; interferons, tumour antigens, IκB, and derivatives of IκB whichlack serine phosphorylation sites (Traenckner, et al., 1995) or whichlack lysine ubiquitinisation sites; glucocorticoid receptors; enzymessuch as catalase, manganese superoxide dismutase, glutathioneperoxidase, LIP members of the C/EBP family such as LIP or LAP(Descombes and Schibler, 1991), ADF (Tagaya, et al., 1989)), genes whichinfluence apoptosis (members of the Bcl-2 family such as Bcl-2,adenovirus E1B19K, Mcl-2; BAX; IRF-2; members of the ICE proteasefamily; variants of cJun, such as TAM-67 (Brown, et al., 1994);adenovirus E1A; p53) and genes which code for other therapeutic proteins(e.g. clotting factors such as factor VIII or IX; growth factors such aserythropoetin; cystic fibrosis transmembrane regulator gene (CFTR);dystrophin and derivatives thereof; globin; the LDL receptor; geneswhich are absent in lysosomal storage dysfunctions such asβ-glucuronidase; etc.).

With regard to the production of cellular tumour vaccines or forpharmaceutical compositions with which the immune response to tumours isto be intensified, the foreign DNA codes for immunostimulating proteinsor tumour antigens or fragments thereof.

The therapeutically active DNA may also code for antisense moleculeswhich prevent the expression of genes or the transcription of specificRNA sequences in the target cell.

With regard to the use of the recombinant CELO virus vector as avaccine, the foreign DNA codes for one or more antigens which bringabout an immune response in the individual treated.

In one embodiment of the invention the foreign DNA codes for an antigenderived from a human pathogen, particularly a pathogen of infectiousdiseases.

Epitopes which can be expressed by recombinant CELO viruses includeepitopes derived from all kinds of human viral pathogens such as HIV,hepatitis A, B, C, hanta virus, polio virus, influenza virus,respiratory syncytial virus, measles, mumps, rubella, papilloma and manyother viruses. The non-viral pathogens include trypanosomes (the causalagents of sleeping sickness and Chagas' sickness), leishmania,Plasmodium falciparum (malaria), various bacterial pathogens such as thepathogens which cause tuberculosis, leprosy, Pseudomonas aeruginosa(complications in cystic fibrosis) and many others.

A summary of vaccines based on mastadenoviruses is given in Table 3; theepitopes mentioned therein by way of example can also be used forinsertion in a vector based on the CELO virus.

With regard to the use of the recombinant CELO virus vector as a vaccinein the veterinary field, e.g. for birds, particularly poultry, theforeign DNA, in another preferred embodiment, codes for an antigenderived from a protein of a pathogen of animal diseases, particularlyinfectious diseases in birds.

Examples of pathogens of bird diseases are Avian Infectious BronchitisVirus (IBV, a corona virus; Jia, et al., 1995; Ignjatovic and McWaters,1991; Kusters, et al., 1990; Lenstra, et al., 1989; Cavanagh, et al.,1988; Cunningham, 1975), Avian Influenza Virus (Orthomyxovirus Type A;Kodihalli, et al., 1994; Treanor, et al., 1991; Tripathy andSchnitzlein, 1991), Fowlpox-Virus (McMillen, et al., 1994), AvianInfectious Laryngotracheitis Virus (Guo, et al., 1994; Scholz, et al.,1993; Keeler, et al., 1991), Mycoplasma Gallisepticum (Nascimento, etal., 1993), Avian Pasteurella Multocida (Wilson, et al., 1993; Lee, etal., 1991; Hertman, et al., 1980; Hertman, et al., 1979), Avian Reovirus(Ni and Kemp, 1992; Huang, et al., 1987), Marek's Disease Virus (MDV;Malkinson, et al., 1992; Scott, et al., 1989), Herpes virus of turkeys(HVT, Herpes virus of Turkeys), Newcastle Disease Virus (NDV; Cosset, etal., 1991; Morrison, et al., 1990), Avian Paramyxovirus Type 1 (Jestin,et al., 1989), Avipoxvirus Isolates (Schnitzlein, et al., 1988), such asJuncopox, Pigeon Pox, and Field-(Field) and vaccine strains of bird poxviruses, Avian Encephalomyelitis Virus (Shafren and Tannock, 1991;Nicholas, et al., 1987; Deshmukh, et al., 1974), Avian Sarcoma Virus,Rotavirus (Estes and Graham, 1985), Avian Reovirus (Haffer, 1984;Gouvea, et al., 1983; Gouvea and Schnitzer, 1982), H7 Influenza Virus(Fynan, et al., 1993).

Apart from DNA sequences which code for therapeutically active geneproducts or for antigens, the foreign DNA may code for proteins orprotein fragments which change the behaviour of the CELO virus,particularly its ability to bind to cells, with regard to the use ofmammals, particularly on mammalian cells. Examples of such proteins arefibre or penton base proteins from mammalian and other adenoviruses,surface proteins of other viruses and ligands which have the ability tobind to mammalian cells and transport the CELO virus into the cells.Suitable ligands include transferrin from various mammalian species,lectins, antibodies or antibody fragments, etc. The skilled person willbe aware of ligands of this kind, other examples can be found in WO93/07283.

The recombinant CELO virus may contain one or more foreign DNAmolecules. These may be inserted either in tandem or spaced apart indifferent sections of the CELO virus sequence.

The foreign DNA is under the control of regulatory sequences; suitablepromoters include for example the CMV immediate early promoter/enhancer,the Rous sarcoma virus LTR, the adenovirus major late promoter and theCELO virus major late promoter.

The suitability of the CELO virus for preparing vectors and theadvantages of these vectors and their applications are basedparticularly on the following properties of the CELO virus:

i) Safety: Naturally, the CELO virus does not replicate in mammaliancells. Therefore, vectors based on this virus can be used in humanswithout any danger of a subsequent infection with a Wild type humanadenovirus complementing the vector and possibly allowing replication.This is an advantage over the Ad2 and Ad5 vectors used at present.

ii) Increased packaging capacity: The CELO virus genome is about 44 kblong, compared with the 36 kb of the Ad5 genome. Both viruses havecomparable virion sizes, so that with a CELO virus vector it is possibleto expand the strict packaging limit of 35 kb which is available withAd5. On the basis of the sequencing carried out within the scope of thepresent invention, DNA-packaging core proteins of the CELO virus wereidentified, and striking differences were found from Ad2 which could beresponsible for the increased packaging capacity. There are about 13 kbat both ends of the CELO virus which would appear not to code forstructural proteins (e.g. capsid components) or for proteins requireddirectly for the virus replication (e.g. DNA polymerase). For theproduction of vectors, these sequences on the CELO virus genome can beremoved and if necessary replaced by complementing cell lines. Thesesequences can be assumed to code for the immune functions or theapoptotic functions (e.g. GAM-1) of the host cell or to be involved inthe activation of the host cell for virus replication (antagonists tothe E1, E3 and E4 regions of Ad2). These are the gene types which areeither non-essential for virus growth in the cell culture, such as theE3 genes of Ad2 (Wold and Gooding, 1991; Gooding, 1992), or which areeasily removed from the virus and can be expressed by a complementingcell line, such as the E1 region in 293 cells (Graham, et al., 1977) andthe E4 region in W162 cells (Weinberg and Ketner, 1983).

iii) Stability: The CELO virion is remarkably stable. Its infectivityand its ability to transport DNA withstand a 30 minute treatment at 60°C. As a comparison, Ad5 loses two powers of ten of its infectivity at48° C. and is completely inactivated at 52° C. Presumably, the CELOvirus did not develop its heat stability naturally, rather this heatstability would indicate a reaction to another type of selectivepressure on the virion. The natural route of CELO virus infection is afaecal-oral route, which requires the virion to survive contact with achemically aggressive environment with extreme pH values and withproteases. For particular applications in gene therapy, a more resistantvirus would be desirable which would survive, for example, in thedigestive tract or in the lungs of a patient suffering from cysticfibrosis.

iv) Targeted use: The CELO virus binds only slightly to mammalian cellson its own and for efficient entry into the cell requires the additionof a ligand (transferrin or lectin; Cotten, et al., 1993). Therefore,recombinant CELO virions are unable to penetrate into human cells,resulting in the following possible applications:

The virus may be genetically modified as stated above in order toexpress, on its surface, ligands which enable targeted transportation,such as for example specific peptides or fibres and/or penton bases ofhuman adenoviruses.

Another possibility is the chemical modification of the virus in orderto couple specific ligands such as transferrin thereto, as proposed forexample in WO 94/24299 and additionally the virus may be biotinylated(WO 93/07283) and bound via streptavidin to biotinylated ligands such aswheatgerm agglutinin or other lectins (WO 93/07283). CELO virus vectorsthus do not have the disadvantages of human adenoviruses which have goodbinding ability to human cells but have to be masked for a specific,targeted use mediated by the ligand.

v) Possibility of use for vaccines: The CELO virus is seldom connectedto diseases in birds, indicating that it provokes a strong protectiveimmune response in bird hosts. The CELO virus vector can easily beadapted for the expression of new vaccine epitopes.

With regard to the removal of regions of the CELO virus DNA, it wasconcluded from the results obtained with the mastadenovirus that, whenthe central sections of the CELO genome are removed, these sections haveto be made available in trans, e.g. by a packaging cell line. Thisrestriction is based on the large quantity of virion components whichare necessary for the assembly of the virus and the need to produce acell line which is capable of producing the corresponding amounts ofthese proteins without any toxicity.

The approaches which have hitherto proved more successful in thisrespect with mastadenoviruses consisted of the production of cell lineswhich express regulatory proteins (E1 and E4 regions) or enzymaticproteins (DNA polymerase, DNA binding protein), because these proteinsare not required in large amounts during a productive virus infection.

Starting from the analysis of the known CELO genes, the sections of thegenome from nt about 12,000 to about 33,000 which code for structuralcomponents of the virus are preferably not interrupted. The region fromabout nt 5,000 to about 12,000 codes for the E2 genes IVa2 (a viraltranscription factor), viral DNA polymerase (POL) and the terminal virusprotein (viral terminal protein; pTP) These genes are essential for thefunction of mastadenoviruses; they ought therefore to be essential forthe CELO virus as well. However, it is theoretically also possible tohave deletions of essential genes of this kind provided that they can beproduced in trans, e.g. by a packaging line. For example, a packagingcell line was prepared which produces Ad5 DNA polymerase, thus making itpossible for this gene to be deleted from the virus genome. A similarprocedure may be used in the construction of CELO virus vectors, byremoving sections or the entire region from nt 5,000 to 12,000 from theCELO virus and having the corresponding functions controlled in trans bya packaging cell line.

Another possible restriction exists with regard to the presumed majorlate promoter, which was provisionally assigned to the region at aboutnt 7,000 (TATA box at nt 7,488). In the mastadenoviruses, this promoteris essential for driving late gene expression. Therefore, any change inthe region at nt 7,000 of the CELO genome must be carried out in a waywhich maintains the promoter function of this region.

Table 4 lists the sequence elements of the CELO virus genome and isdivided into various categories with regard to their deletion and/ormutation in the production of CELO virus vectors (in Table 4 L1, L2,etc. denote “late message 1, 2, etc., corresponding to the nomenclaturenormally used for mastadenoviruses):

Category 1 includes sequence elements which are required in cis andtherefore cannot be made available in trans by a complementing cell lineor by a complementing plasmid. These sections are necessary and aretherefore present on the CELO virus according to the invention; theseare the left and right terminal repeats and the packaging signal.

Sequences of category 2 code for proteins which are required in largeamounts for virion production. These proteins may optionally be producedby a gene contained in a complementing cell line or on a complementingplasmid. Other sequences of category 2 are the major later promoter, thetripartite leader sequence and also the splice acceptor sites (SA) orthe polyadenylation sites (poly A sites) of genes which are essentialand which cannot be made available in trans.

Fundamentally, care must be taken to ensure that, in modifications ofthe CELO virus DNA which are carried out at the boundaries of genes, anycontrol signals present, e.g. polyA sites are not interrupted oraffected in any other way if possible.

The genes deleted from the CELO virus or non-functional genes thereinmay be prepared in trans, e.g. by complementing cell lines.

Complementing cell lines (“helper cells”) can be prepared by the mannerknown from the literature, analogously to helper cells which complementthe functions of mammalian adenoviruses. To do this, the relevant CELOvirus gene on a plasmid, preferably combined with a selectable marker,is introduced into cells which permit the replication of CELO virus,preferably into immortalised cell lines such as LMH (Kawaguchi, et al.,1987) or immortalised quail cell lines, as described for example byGuilhot et al., 1993. In helper cells which express the relevant CELOvirus genes, optionally stably integrated, the defective CELO virusesare able to replicate.

Instead of making the regions of the CELO virus deleted in the vectoravailable by means of a cell line, the deletions may also becomplemented by a copy of the relevant gene contained on a plasmid. Forthis, the method described in WO 96/03517, that described by Cotten etal., 1994a and 1994b) or the one described by Wagner et al., 1992, maybe used, for example, in which a CELO virus vector containing a deletionis inserted, as a component of a transfection complex, containing aconjugate of polylysine and a UV/psoralen-inactivated adenovirus (humanor CELO) and optionally transferrin-polylysine, into embryonic chickenkidney cells or liver cells, embryonic or immortalised quail cells, e.g.liver or kidney cells, and the transfection complex also contains aplasmid which carries a copy of the gene or genes which lack the CELOvirus vector. The combination of genes contained on the vector and genescarried by the plasmid results in a normal virus replication cycle.(Similar approaches were used in mastadenovirus systems in order tocomplement E1-deficient adenoviruses (Goldsmith, et al., 1994) andE4-deficient adenoviruses (Scaria, et al., 1995)). The subsequentamplification of the virus may be carried out by using the defectivevirus as a carrier which is dependent on the complementing plasmid usingthe methods described above.

Another possible way of replacing the genes missing from the CELO virusis by using helper viruses.

The helper virus used may be a CELO virus (Wild type or partlydefective). In this embodiment the CELO plasmid carrying the mutation(e.g. a derivative of pCELO7), is introduced into chicken cells, e.g.using the method described in WO 96/03517 or described by Cotten et al.,1994, using as the carrier for the derivative, for example,psoralen/UV-inactivated adenovirus (human or CELO) together with anadenovirus (human or CELO) as a carrier for the plasmid or plasmids withthe genes which complement the defect. Alternatively, a Wild type CELOvirus may be used both as a carrier and as source for complementing genefunctions. The subsequent amplification of the defective CELO virusesobtained is carried out by co-infection of the defective CELO virus witha complementing adenovirus (e.g. Wild-type CELO or a CELO which hasmutations at other points of the genome).

CELO virus genes of category 3 include the sequences on Sections A, Band C. These are sequences which code for a protein or an RNA moleculewhich is necessary for the interaction with the host cell machinery orwith the host immune system. These proteins should be required in fairlylow concentrations or may be dispensable for cultivation of the virus inthe tissue culture.

Thus, preferably, in the CELO virus vectors according to the inventionthe genes of category 3 are replaced by the gene in question; ifnecessary, complementary cell lines or plasmids or helper viruses can beprepared which produce the corresponding gene products.

In one embodiment of the invention the vectors according to theinvention contain the gene in question instead of one of the fibregenes. The CELO virus has two fibre proteins (Laver, et al., 1971;Gelderblom and Maichle-Lauppe, 1982; Li, et al., 1984a). It can beassumed that one of the fibres of the CELO virus is not necessary forthe assembly of the virion and the infectivity. This assumption isbacked up by electron microscopic observations that the longer fibre(fibre 1) should associate with the penton base along the side of thecomplex, whilst the shorter fibre (fibre 2) projects out of the middleof the penton base, similarly to the penton/fibre complexes in themastadenoviruses (Hess, et al., 1995). In adenoviruses with only asingle fibre, the fibre molecule is required for the assembly of thevirus; in the absence of fibres no stable mature viruses are formed. TheCELO virion should therefore require fibre 2 for stability and as aligand, whereas fibre 1 acts only as a ligand. Within the scope of thepresent invention the assumption that, of the two fibre genes of theCELO virus, fibre gene 1 located in region C is superfluous and can bereplaced by the gene in question was proved correct by removing thefibre 1 gene and replacing it with a luciferase expression unit.

Other-examples are inserts in region A and/or B.

Within the scope of the present invention it was found that destructionof the reading frame at nt 794 (region A) which codes for dUTPase yieldsviable viruses. The dUTPase gene is thus a gene which is not necessaryfor growth in cell culture.

In one embodiment of the invention, the recombinant CELO virus thuscontains a foreign gene which is inserted in the region of the readingframe coding for dUTPase.

According to another aspect the present invention relates to a processfor preparing recombinant CELO virus.

The process is characterised in that the CELO virus genome contained ona plasmid or sections thereof is or are genetically manipulated.

In one aspect of the invention the genetic manipulation consists ofinsertion and/or deletion. Insertions and/or deletions can be carriedout by using restriction enzyme cutting sites which occur naturally inthe CELO virus DNA in these sections, e.g. the FseI cutting siteoccurring at position 35,693 in Section B. The insertion may be carriedout directly into this cutting site or beyond this cutting site or closeto this cutting site, or this cutting site may be used to allowrecombination in the surrounding area.

In one preferred embodiment the manipulation consists of carrying outinsertions and/or deletions using standard methods of molecular biology(Maniatis, 1989). The naturally occurring restriction cutting sites canbe used for this, e.g. sites located in regions of the genome which arenon-essential for cultivation of the virus in the host cell, e.g. theFseI cutting site which occurs at position 35,693 in Section B. Theinsertion can be made directly into this cutting site or beyond thiscutting site or in the vicinity of this cutting site, or the cuttingsite may be used to facilitate recombination in the surrounding area.Foreign DNA sequences can be inserted, e.g. marker genes or genes codingfor therapeutically active proteins.

An alternative possibility is to remove CELO sequences which are flankedby two restriction sites and replace them with new sequences. (Anexample of this is dUTPase mutation as carried out in Example 7.) Inthese cases the manipulation is carried out with the entire CELO virusgenome. In the event that restriction sites are present, thedeletion/insertion can alternatively be carried out on a subfragmentwhich is then re-incorporated in the entire genome by ligation andoptionally recloning in bacteria.

Another possibility is to insert the foreign gene in artificialrestriction enzyme cutting sites produced by conventional methods ofrecombinant DNA technology (Maniatis, 1989).

In one embodiment the process is characterised in that manipulations arecarried out in a plasmid DNA which contains the CELO virus genome, inCELO DNA sequences, with the exception of the left and right invertedterminal repeats and the packaging signal.

In another preferred method, the manipulation of the CELO genome iscarried out by recombination. For this, a subfragment of the CELO genomeis manipulated in order to introduce mutations and/or new sequences.Subfragments can be prepared by various methods, specifically by PCR(polymerase chain reaction), by ligation between PCR products or betweenrestriction fragments or by subcloning in bacteria (as described in theExamples of the previous invention; see also Chartier et al., 1996).Examples of suitable bacteria strains for recombination are BJ 5183(Hanahan, 1983) or JC 8679 (Gillen et al., 1974) or JC 5176(Capado-Kimball and Barbour, 1971).

For recombination using PCR products, the sequence to be inserted intothe CELO genome is prepared by PCR (Oliner et al., 1993) using primerswhich flank the sequence plus about 15 nucleotides of the sequencecomplementary to the insertion site in the CELO genome. In a secondround of PCR, another 15 nucleotides are hung from the sequencecomplementary to CELO, resulting in a PCR product which consists of thesequence to be inserted with 30 nucleotides of the CELO sequence at eachend. This fragment is mixed with a plasmid which contains the CELO DNA(e.g. the plasmid pCELO7 prepared within the scope of the presentinvention) and which has been linearised with a restriction enzyme whichcuts only between the two flanking sequences hung from the sequence byPCR.

For recombination using ligation reaction products (prepared byconventional techniques as described for example by Maniatis et al.,1989), in principle the same procedure is used as in the recombinationwith cloned fragments, except that the intermediate cloning step isomitted.

In every case, the manipulated product obtained is characterised andused to prepare virus by transfecting avian cells (e.g. using the methoddescribed by Wagner et al., 1992; Cotten et al., 1994; or Cotten et al.,1993) and then cultivating them, after which the virus is harvested.

For preparing recombinant CELO virus using cloned fragments, the methodpreferably comprises subcloning a small fragment from the relevantregion of CELO virus into which the foreign gene is to be inserted on abacterial plasmid in order to ensure that restriction sites which occurseveral times on the CELO virus genome occur only once on the plasmid.These restriction sites are used to remove a region from the smallfragment. For preparing the CELO virus vector this region is replaced byforeign DNA. The foreign DNA may consist solely of a linker with arestriction site occurring only once or of a sequence coding for aprotein or for an antigen. The sequence may also code for a reportergene with a restriction site occurring only once. This makes furthermanipulation of the CELO virus easier by inserting the foreign DNA,which codes for a therapeutically active gene product or for an antigen,into this restriction site, and at the same time the reporter genepermits rapid information as to the efficiency of the vector, byintroducing the plasmid into cells and monitoring the expression of thereporter gene.

SUMMARY OF THE FIGURES

FIG. 1A: Comparison of the genomic organisation of Ad2/5 with the CELOvirus

FIG. 1B: Restriction map of the CELO virus genome

FIGS. 2A and B: Pulsed Field gel-electrophoretic analysis of the genomesize of adenoviruses

FIG. 2C: Characterisation of plasmid-cloned copies of the CELO virusgenome by means of restriction endonucleases

FIG. 3: Dot matrix analysis of the DNA sequence homology between CELOvirus and Ad2

FIG. 4: Amino acid sequences of protein VII and pX from variousmastadenoviruses compared with CELO virus and the core proteins core 2and core 1

FIG. 5: Construction of a plasmid which contains the entire length ofthe CELO genome

FIG. 6: Preparation of a CELO vector from a copy of the CELO virusgenome contained on a plasmid

FIG. 7: Identification of bacterial clones which contain a deletion inthe dUTPase gene

FIG. 8: Comparison of Wild-type CELO and CELO containing a deletion inthe dUTPase gene by Western blot analysis.

In the Examples, the following materials and methods were used unlessotherwise specified:

a) Virus and virus DNA

A plate-purified isolate from CELO virus (FAV-1, Phelps strain) whichwas used as starting material for the DNA both for direct sequencing andfor the formation of bacterial plasmid clones, was grown in 9 day oldpathogen-free chicken embryos, as described by Cotten, et al., 1993. TheFAV-1 isolates OTE (Kawamura, et al., 1963) and Indiana C (Calnek andCowen, 1975; Cowen, et al., 1978) were cultivated in chicken embryokidney cells. The virus was purified from the allantoic fluid or frominfected embryo kidney cells by separation in CsCl gradients, asdescribed by Laver, et al., 1971, and Cotten, et al., 1993. Virus DNAwas isolated by treating the purified virions with proteinase K (0.1mg/ml) and SDS (0.2%) at 56° C. for 45 min and subsequent equilibriumcentrifugation of the DNA in a CsCl gradient in the presence of ethidiumbromide. After the second gradient, the ethidium bromide was removed byextraction with CsCl-saturated isopropanol and the virus DNA wasexhaustively dialysed against 10 mM Tris, 0.1 mM EDTA, pH 8.

b) Chicken embryo kidney cells

The kidneys of 14 day old chicken embryos were collected washed in PBSand digested with pancreas trypsin (2.5 mg/ml in PBS) at 37° C. Thedispersed cells were mixed with an equal volume of foetal calf serum,the cells were collected by centrifugation, washed once with FCK mediumand taken up in the same medium again. (The FCK medium is medium 199with Earle's salts (Sigma M2154) supplemented with 10% tryptosephosphate (Sigma T8159), with 10% foetal calf serum, 2 mM glutamine, 100μg/ml streptomycin and 100 IU/ml penicillin.) The cells were plated outin 175 cm² tissue culture flasks (2 embryo kidneys per flask), stored at37° C. under 5% CO₂ and infected 24 to 48 hours later. The cells wereinfected with about 1,000 virus particles per cell and harvested 3 to 4days after infection when the cytopathic effect was complete.

c) Pulsed Field Electrophoresis

Aliquots of purified adenovirus DNA (10-20 ng) were loaded onto a 1%agarose gel (BioRad, PFC agarose) and separated using a BioRad CHEFMapper Pulsed Field Electrophoresis system (FIGE mode) for 24 hours in0.5×TBE cooled to 14° C. The switching time, both in the forwarddirection and in reverse, was changed logarithmically from 0.22 secondsto 0.92 seconds with a ramp factor of 0.357 (21%). The forward voltagegradient was 9 V/cm (300 V), the reverse voltage gradient was 6 V/cm(200 V). After the run the gel was stained for 25 minutes in 0.5 μg/mlof ethidium bromide solution in water and then destained for 1 hourbefore the DNA pattern was made visible under UV light.

d) Sequencing methods, data analysis

For the sequencing, EcoRI and HindIII restriction fragments of CELOvirus DNA were cloned in pBlueScript SK(−). Three of the EcoRI clonescontaining the EcoRI fragments C, D and E (see FIG. 1B) and five of theHindIII clones containing the HindIII fragments F, A, G, B and E (cf.FIG. 1B, were selected for the preparation of deletions in one directionusing exonuclease III (in FIG. 1B the cleavage sites for the restrictionenzymes EcoRI, HindIII, BamHI and BgIII are given; the alphabeticalnames for the EcoRI and HindIII fragments, on the basis of theirrelative sizes, are also given). These deletion clones were sequencedusing the Taq Dyedeoxy Terminator system with the automatic sequencingapparatus ABI 373 according to the manufacturer's instructions. Thesequence analysis of the terminal 2,000 bp at the left hand end and the1,000 bp at the right hand end of the CELO virus genome, the sequencingto close the gaps between the fragments EcoRI C/HindIII G and thefragments HindIII B/EcoRI D and the sequencing to confirm the sequenceat various points of the genome were carried out by direct sequencing ofthe viral DNA. All the sequence data are the results of at least threesequence reactions. The sequence data were combined using the programsSeqEd (ABI) and SeqMan (Lasergene). The sequence analysis was carriedout using the program GCG of the University of Wisconsin.

EXAMPLE 1

Preparation of a recombinant bacterial plasmid clone of the CELO virusgenome

a) Preparation of a plasmid vector with a low copy number for cloningthe CELO virus

The bacterial vector pBR327 (ATCC No. 37516) was chosen for this becauseit is retained in bacterial host strains at relatively low copy numbers(instead of this plasmid any other plasmid with a low copy number suchas pBR322 could be used equally well). It was essential to create on thevector a restriction site which occurs only once and which does notappear in the CELO virus sequence. As described hereinafter, the virussequence has to be cut from the plasmid vector sequences in order toinject a productive infection; therefore, restriction sites which flankthe CELO sequence (but which are not present within the CELO sequence)have to be incorporated in the vector. In the experiments carried out,the restriction enzyme SpeI was used; however, any other enzymes whichdo not have recognition sites in the CELO sequence, such as AscI, PacIand SfiI, may be used instead.

The plasmid p327SpeI was prepared by ligating an SpeI linker (NewEngland Biolabs) into the Klenow-treated EcoRI site of pBR327, therebydestroying the EcoRI site and creating an SpeI site which occurs onlyonce.

b) Cloning the ends of CELO

The two terminal HindIII fragments were cloned. In order to do this,CsCl-purified genomic CELO DNA was digested with HindIII and separatedon a low-melting agarose gel (0.7% low melting agarose in TAE). The 1601bp left hand end fragment and the 959 bp right hand end fragment werecut from the gel, and each gel fragment was suspended in 300 μl of 10 mMTris, 1 mM EDTA pH 7.4 and heated to 70° C. for 10 min to melt theagarose. The terminal peptides were eliminated by the addition of NaOHto 0.3 N and heating to 37° C. for 90 min. (Hay, et al., 1984). Thesolutions were then cooled to ambient temperature, then Tris pH 7.4 (to0.1 M) and HCl (to 0.3 M) were added in order to neutralise the NaOH.The fragments were heated to 56° C. for 20 min. and slowly cooled (over1 hour) to ambient temperature in order to facilitate re-annealing. Thenthe DNA was purified over a Qiaquick column and ligated for 4 hours at16° C. using a Pharmacia T4 ligase reaction (New England Biolabs) to anSpeI linker (New England Biolabs). The ligase was inactivated by heatingto 70° C. for 10 minutes, excess linker was removed (and an overhangcomplementary to SpeI was formed) by digesting for 2 hours withrestriction endonuclease SpeI. The DNA fragments were in turn purifiedby Quiquick column chromatography and ligated to p327SpeI treated withSpeI/HindIII/calf alkaline phosphatase. The ligation product wastransformed into the bacterial strain DH5alpha, and plasmid clones wereidentified which carried either the 1601 bp left hand end fragment orthe 959 bp right hand end fragment (both released by SpeI/HindIIIdigestion). In order to confirm the terminal 300 bp of both fragments,DNA sequence analysis was carried out.

c) Cloning of both CELO ends on the same plasmid

The 1601 bp left hand end and the 959 bp right hand end fragment werecut from their vectors by HindIII/SpeI digestion, separated by gelelectrophoresis and purified by Qiaquick chromatography. The twofragments were mixed in approximately equimolar amounts and ligated for30 minutes using the Pharmacia T4 ligase reaction. An aliquot ofSpeI/CIP-treated p327SpeI was added and ligation was continued for 4hours. The ligation mixture was transformed in DH5alpha and plasmidclones were identified which carried the correct double insert (pWu#1and pWu#3).

The second HindIII site was removed by cleaving pWu#3 with ClaI andBamHI, treating with Klenow enzyme, religation, transforming DH5alphaand selecting a clone which missed the ClaI/BamHI fragment (which hadcontained a HindIII site). The resulting plasmid designated pWu-H35 nowcontained a single HindIII site between the left and right hand CELO endfragments.

d) Cloning the entire CELO genome

The plasmid pWu-H35 obtained in c) was treated with HindIII and CIP andpurified on a low melting agarose gel following by Qiaquickchromatography. The linearised vector pWu-H35 was mixed with 0.3 μg ofpurified CELO virus DNA, then 30 μl of electro-competent bacterialstrain JC8679 (Gillen, et al., 1974; Oliner, et al., 1993) were added tothe DNA mixture on ice. 10 Minutes later the mixture was transferredinto a BioRad Electroporation chamber and pulsed with an electric chargeof 2.4 kV (BioRad Gene Pulser; Oliner, et al., 1993). The bacteria werethen plated onto LB ampicillin plates and the ampicillin-resistantcolonies were investigated for their plasmid content. Recombinationbetween the terminal CELO sequences on pWu-H35 and the ends of thegenomic CELO DNA re-establishes the circularity of the linearisedplasmid and allows growth on ampicillin. A plasmid which contains theCELO genome over its full length was identified, and this plasmid,referred to as pCELO7, was used for the subsequent investigations. FIG.2C shows the characterisation of plasmid-cloned copies of the CELO virusgenome. Plasmid DNA from clones designated pCELO7, 8, 9 and 13 or DNAisolated from purified CELO virus, was digested either with BglII(tracks 2-6) or HindIII (tracks 7-11) and separated on a 0.6% agarosegel, and the DNA was shown up by ethidium bromide staining. Themolecular weight marker (tracks 1 and 12) was bacteriophage λ-DNA cutwith HindIII and EcoRI. The sizes of some molecular weight fragments (inbase pairs) are shown on the right of the Figure. For each enzyme, thetwo CELO end fragments which are bound to the bacterial plasmid duringcloning (and which are therefore not released after restrictiondigestion) are given on the left of the Figure (in base pairs). Theseare the fragments with 5832 and 5102 bp with BglII or 1601 and 959 withHindIII.

The construction of pCELO7 is shown in FIG. 5.

e) Initiation of a CELO virus infection by a cloned CELO genome pCELO7was cleaved with SpeI (which cleaves at the sites flanking theadenovirus termini), extracted with phenol/chloroform and passed over anHBS-equilibrated gel filtration column. (Pharmacia Nick column) toremove any impurities. The cleaved DNA was then incorporated instreptavidin-polylysine/transferrin-polylysine/biotin-adenovirus(UV/psoralen-inactivated) as described in WO 93/07283. Complexescontaining 0.5 μg of SpeI-cleaved pCELO7 plus 5.5 μg of carrier DNA(pSP65; Boehringer Mannheim) were used to transfect primary embryonicchicken kidney cells (the complexes contain 4 mg of DNA per 180 cm²flask, containing about 3×10⁶ cells), and the cells were investigatedfor the cytopathic effect caused by virus replication. Five days aftertransfection, when the majority of the transfected cells had beenrounded off and detached from the surface of the plate, the cells wereobtained by centrifuging and the CELO virus was purified as described byCotten, et al., 1993. The virus yield from plasmid cloned CELO virus iscomparable with the yields obtained by using pure CELO virus DNA(purified from virions).

EXAMPLE 2

Preparation of a CELO mutant which lacks the sequences from nt 35,870 to42,373 at the right hand end

There are no identifiable viral structural genes beyond the two fibregenes with the L5-polyadenylation site at position 31771. (There is acryptic VA-gene at positions 39,841 to 39,751.) Investigations weretherefore carried out to see whether the sequences between about 32,000and the right ITR are necessary for the growth of the virus in cellculture. For this an accumulation of seven AseI sites were used atpositions 35,870, 36,173, 38,685, 38,692, 39,015, 42,348 and 42,373,which does not appear anywhere else in the CELO virus genome. pCELO7 wasdigested with AseI, religated and a plasmid which lacked the inner AseIfragments was identified and designated pALMCELO_(—)35870-42373. Inconnection with this it should be noted that the plasmid vector also hasan AseI site; however, this is located in the ampicillin resistancegene, and selection for ampicillin resistance requires that all positivecolonies have at least the two fragments which carry the right and lefthand halves of the amp gene.

To aid further manipulations of the virus with the missing left hand endof the genome, pALMCELO_(—)35870-42373 was digested with AseI (whichcuts once in the ampicillin resistance gene of the plasmid and once atposition 35,870) and ligated to a linker oligonucleotideTACCCTTAATTAAGGG which codes for a cutting site for the restrictionendonuclease PacI and for ends which are complementary to those formedduring AseI digestion. Religation, followed by selection for ampicillinresistance, identified plasmids which did not integrate theoligonucleotide at the AseI site of the ampicillin resistance gene.Restriction digestion identified a plasmid which carried a PacI site atthe earlier AseI site of CELO at position 35,870. The plasmid wasdesignated pALMCELO_(—)35870-42373P.

EXAMPLE 3

Preparation of a CELO virus vector in which a fibre gene is missingwhich is replaced by a gene of interest

The CELO fibre genes are contained on a HindIII fragment which extendsfrom nt 27,060 to 33,920 (the HindIII B-fragment, cf. the restrictionmap in FIG. 1B). On this fragment the sequence coding for fibre 1extends from nt 1,054 to 3,435. The 5H3 fragment was digested with BglII(which cuts at nt 1,168) and HpaI (which cuts at 3,440), the BglII endwas filled with Klenow enzyme and ligated to a bluntCMV/luciferase/β-globin cleavage/polyadenylation signal fragment fromthe plasmid pCMVL (Plank et al., 1992) to form the plasmidp5H_(—)28227-30502(luc) which lacks almost the entire fibre 1 sequencewhich is replaced by a luciferase expression unit.

The relevant restriction cutting sites in CELO are as follows:

BglII A′GATC_T Cuts at: 0 5102 15979 23472 28227 37972 43804 Size: 510210877 7493 4755 9745 5832 HindIII A′AGCT_T Cuts at: 0 1601 5626 1788123327 27060 33920 38738 42845 42845 43804 Size: 1601 4025 12255 54463733 6860 4818 4107 959 HpaI GTT′AAC Cuts at: 0 5503 20673 23355 3050243804 Size: 5503 15170 2682 7147 13302 NotI GC′GGCC_GC Cuts at: 0 1738943804 Size: 17389 26415 XbaI T′CTAG_A Cuts at: 0 1659 1988 28608 3926841746 43804 Size: 1659 329 26620 10660 2478 2058

The modifications which were carried out on p5H_(—)28227-30502(luc) wereintroduced into the entire CELO genome in the following manner: TheCELO/luciferase/CELO fragment was cut from p5H_(—)28227-30502(luc) as aHindIII fragment. This fragment was recombined with the 26 kb XbaIfragment (CELO nucleotides 1988-28608) and the terminal HpaI fragmentsderived from pCELO7 (obtained by cutting with HpaI, containing the lefthand end of the CELO virus and pBR327 sequences, defined by the HpaIsites). The three DNA fragments (each about 50 ng) were mixed in waterand electroporated in JC8679 cells as described above.

EXAMPLE 4

Insertion of a reporter gene (luciferase) in the CELO genome

i) Preparation of a left hand end fragment containing a CMV luciferaseconstruct

The EcoRI fragment designated 7R1 (nucleotides from positions 79 to8877) was cloned into a pSP65 derivative designated pAAALM (described inWO 95/33062). The plasmid was transformed into the DAM methylasenegative bacterial strain JM110 in order to allow cleavage of the ClaIsites in the fragment. The plasmid was purified, cut with ClaI (atposition 1083) and NcoI (at position 4334), treated with Klenow enzymeto fill the overhanging ends and ligated to a bluntCMV/luciferase/β-globin cleavage/polyadenylation signal (Plank et al.,1992). The resulting plasmid was designated p7R1_(—)1083-4334Luc.

ii) Recombination of the luciferase left hand end fragment into acomplete (full length) CELO sequence

The plasmid p7R1_(—)1083-4334Luc was cleaved with Eco47 III, whichcleaves at the CELO nucleotides 937, 1292, 2300 and 8406 (the sites atnucleotide 1292 and 2300 are absent from p7R1_(—)1083-4334Luc) in orderto release a large fragment containing the sequenceCELOnt937-1083/CMVLusPA/CELOnt4334-8406. This fragment was recombined inpCELO7. pCELO7 was cleaved at the single PmeI site at CELO nt7433 andexhaustively dephosphorylated with calf intestinal phosphatase. Thelinearised pCELO7 was mixed with an approximately 3 to 5 molar excess ofCELOnt937-1083/CMVLucPA/CELOnt4334-8406. The mixture was electroporatedinto the bacterial strain JC8679 and ampicillin-resistant colonies wereexamined on plasmids which contain the desired recombinant DNA. Thecorrect plasmid was identified, characterised by restriction enzymeanalysis and designated pCELOLucI.

iii) A CELO virus expressing luciferase was prepared by transfectingpCELOLucI into primary embryonic chicken kidney cells as describedabove.

EXAMPLE 5

Preparation of a CELO vector from a copy of the CELO virus genomecontained on a plasmid

The region between the DraIII site (originally contained at nt 34,426 inthe CELO virus genome) and the XhoI site (originally contained at nt36,648 in CELO virus genome) were removed from the plasmid pAALMH3 whichcontains the HindIII fragment from nt 33,920 to nt 38,738, cloned inpAALM. Then it was treated with T4-DNA polymerase to produce blunt endsand ligated with the CMV/luciferase/β-globin fragment (cf. Example 4).In this way the plasmid p7H3Δ34426-36648 Luc was obtained. TheCELO/luciferase/CELO fragment was cut on a HindIII fragment and insertedinto the CELO genome of pCELO7 by recombination via the FseI siteoccurring only once at position 35,694. This yielded the plasmid pCELOΔ34426-36648Luc. Digestion with SpeI and transfection into embryonicchicken kidney cells yielded a virus CELOΔ 34426-36648Luc. Then furtherinsertions were carried out replacing the luciferase sequence with othergenes of interest, using the once occurring PacI site which wasintroduced with the luciferase sequence.

FIG. 6 shows the cloning strategy used in this Example in general form:a small CELO fragment is subcloned into a plasmid (containingrestriction site C); the restriction sites A and B which occur only oncein this plasmid are used to replace the sequence with foreign DNA. Asthe next step, the entire fragment containing the foreign DNA betweenCELO sequence is cut from the plasmid and mixed with the plasmid whichcontains the entire CELO DNA and which has been cut with a restrictionenzyme (D) which cleaves the CELO-DNA only once. With this mixture,bacteria (e.g. of the strain JC8679; Oliner et al., 1993; or anotherbacterial strain with a similar capacity for recombination) aretransformed; recombination yields the desired plasmid containing theforeign DNA as an insert in the CELO virus genome.

EXAMPLE 6

Preparation of a quail cell line which complements the 7R1 deletionsand/or the 9R1 deletions in CELO

The plasmids pX7R1 and pX9R1 (described in WO 95/33062) were introducedinto primary embryonic quail kidney or liver cells by transferrinfectionas described in WO 93/07283. Four days after transfection the cells weretrypsinised and seeded at ⅕ of the original density. The cells were fedtwice a week with FCK medium. Clonal lines were expanded and cloneswhich carried either the 7R1, 9R1 plasmid or both plasmids wereidentified by PCR analysis. The RNA expression of the integratedplasmids was determined by Northern analysis.

EXAMPLE 7

a) Preparation of a CELO virus genome with a mutation in the ORF₇₉₄dUTPase gene

A plasmid designated pWuΔdut was produced by removing a 540 bpAflIII-SacI fragment from the ORF₇₉₄ in pWu-H35 (see Example 1 c). Inorder to product pCELOΔdut, pWuΔdut was linearised with HindIII anddephosphorylated using alkaline shrimp phosphatase. After gelpurification the DNA was mixed with purified CELO DNA and used totransform E. coli BJ5183 (Degryse, 1996) to ampicillin resistance. Fromthe ampicillin resistant bacterial colonies obtained the DNA wasextracted and E. coli DH5a was transformed therewith. DNA extracted fromthese bacteria was analysed by restriction mapping in order to identifyrecombinant virus plasmids. The identity of the clones was determined byrestriction mapping (FIG. 7; pWu-H35 is designated “pWu” in the Fig.).The digestion of the Wild type plasmid pWu-H35 with HindIII and SpeIyields fragments of 2944 bp, 1607 bp and 961 bp (track 2). The deletionwhich changes the dUTPase converts the 1607 bp fragment into a 1071 bpfragment (track 3; the modified fragments are marked with an asterisk).The plasmids which contain the complete sequence coding for CELO or thecomplete CELO sequence plus the dUTPase mutation were analysed bySpeI/HindIII digestion and showed the same change of the 1607 bpfragment into a 961 bp fragment (tracks 4 and 5).

b) Preparation of recombinant CELO clones from chicken cells

Either 6 μg pCELO7 (see Example 1 d) or 6 μg of pCELOΔdut (see above,digested with SpeI) were used to transfect primary embryonic chickenkidney cells (approximately 500,000 cells in a 2.5 cm well) usingpolyethylene amine (PEI)/adenovirus complex. For this, theQiagen-purified DNA was extracted with Triton X-114 in order to removelipopolysaccharide as described by Cotten et al., 1994. Transfectioncomplexes were prepared by diluting 6 μg of digested DNA in 250 μl of 20mM HEPES, pH 7.4. 20 μl of 10 mM PEI (molecular weight 2,000, pH 7) werediluted in 250 μl of 20 mM HEPES, pH 7.4. The PEI solution was addeddropwise to the DNA solution, incubated for 20 minutes at ambienttemperature and then mixed with 1.5 μl of an adenovirus preparation(psoralen/UV-inactivated adenovirus type 5, cf. WO 1719, 1.5×10¹²particles/ml). After another 20 minutes the complex was added to thecells in DMEM without serum (250 μl of complex to 1.25 ml of medium).The medium was changed for normal growth medium (with serum) and 4 to 5days later the cells were harvested, taken up again in 100 μl of HBS andsonicated for 2 minutes. A 10 μl aliquot of this sonicate (virus inpassage 1) was used to infect the same number of primary embryonicchicken kidney cells in a 2.5 cm well in a cell culture plate. Afteranother 4 to 5 days the cells were counted in order to determine thecytopathic effect (CPE end point assay or plaque assay, Precious andRussel, 1985). The cells were harvested (virus in passage 2) as in thefirst step and used to infect fresh chicken cells; harvesting thesecells yielded viruses of the third passage, the analysis of which isshown in FIG. 8.

c) Western blots

The virus infected cells were harvested, taken up in HBS and sonicated.Aliquots were mixed with 5×charging buffer (250 mM Tris-Cl, pH 6.8, 500mM DTT, 10% SDS, 0.5% bromophenol blue, 50% glycerol), heated to 95° C.for 3 minutes and then allowed to run in a 10% polyacrylamide gel. Theproteins were transferred onto nitrocellulose, blocked overnight in 5%skimmed milk/TBST (10 mM Tris-Cl, pH 7.4, 150 mM NaCl, 0.05% Tween 20).Viral proteins were shown up using anti-CELO-antisera from rabbits(1:1000) and anti-rabbit-horseradish peroxidase (DAKO; 1:20000) and madevisible by ECL (Amersham). CELO virus (2.5×10¹² virus particles/ml) wasused as the control. The rabbit serum was prepared using CsCl-purifiedCELO virus and heat-inactivated at 60° C. for 30 minutes.

d) Extraction of virus DNA

Virus infected cells were harvested and taken up in 100 μl of HBS/0.1%SDS/1 g/ml proteinase K, incubated for 1 hour at 56° C. and extractedwith phenol/chloroform. The DNA was precipitated with ethanol.

The analyses carried out showed that recombination between thelinearised plasmid pWuΔdut and the CELO DNA yielded two types ofplasmids. Recombination to the left hand end of the dUTPase mutationyielded a Wild type CELO genome; recombination on the right hand side ofthe dUTPase mutation yielded a CELO genome which carried the dUTPasemutation.

The infection of primary embryonic chicken cells both with CELO DNA andwith CELO-Δdut-DNA produced cytopathic effects which took the form ofswollen, detached cells after 36 hours, whereas control cells (treatedwith lysates of cells which had been transfected with an empty vector(Bluescript pBS, Stratagene)) remained healthy in their morphology.

Western blot analysis showed that CELO viruses and CELO Δdut virusesproduced by plasmid DNA are indistinguishable from Wild type virus grownin fertilised, 9 day old hens eggs.

In all, the tests carried out in this example show that pCELO7 codes aviable CELO virus genome. After excision with SpeI and transfection intoprimary embryonic chicken kidney cells this DNA yields infectious,passagable virus. Lysates of viruses of the 1st and 2nd passage producea cytopathic effect on primary embryonic chicken kidney cells. It shouldbe noted that these lysates were produced by sonication, which rules outthe possibility that the CPE in the secondary and tertiary infectionscan be put down to the expression of viral genes which originates fromthe residual plasmid DNA in the lysates; plasmid DNA cannot be expectedto withstand the method used to produce the lysates. In addition, it wasfound that with each round of infection there is a 100 foldamplification of the agent which causes CPE; this conforms to theamplification of a virus but not to the single passage of residualplasmid DNA from the first transfection.

The deletion of 540 bp in the CELO genome with which sequences betweenan AflIII site at bp 609 and a SacI site at bp 1145 were removed and theopen reading frame coding for dUTPase was destroyed, yielded a virusgenome which is viable even in primary embryonic chicken cells. With theUTPase gene a virus gene was thus identified which is not necessary forgrowth in cell culture.

TABLE 1 CELO virus Sequences, published or from data banks differencesbetween published data bank coordinates in sequences and new sequenceaccession # authors, publication size the sequence (GenBank Accession #U46933) remarks Aleström, et al, 1982b  101 bp  1-101 7 bases different5′ITR K00939 Shinagawa, et al, 1983  68 bp  1-68 7 bases different 5′ITRZ17216, Akopian, et al., 1992 3576 bp   1-3576 3 bases different 92-100%labelled S61107 1 missing base slight differences in 3 additional basesthese 2 versions Z48167 unpublished 3433 bp 13597-17033 6 basesdifferent contains genes for 4 missing bases penton base and core 1additional base proteins L13161 Cai, et al., 1993  900 bp 21023-21922 nodifferences contains protease gene X84724 Hess, et al., 1995 7359 b 27060-34299 2 bases different contains genes for 6 missing bases pVIII,fibre 1, fibre 2 3 additional bases 11 (GCA) repeats (new sequence shows9) 6 doubtful bases M12738 Larsson, et al., 1986  440 bp 39584-40023 nodifferences contains VA gene Z22864 unpublished 3670 bp 35235-38905 2bases different assigned by the 4 missing bases authors: 11.2-19.2% 2additional bases X17217 Akopian, et al., 1990 4898 bp 38906-43804 2bases different assigned by the authors: 11.2% K00940 Shinagawa, et al,1983  68 bp 43741-43804 7 bases different 3′ITR Aleström; et al., 1982b 124 bp 43680-43804 2 bases different 3′ITR 1 missing base

TABLE 2A Organisation of the CELO Virus Genome Cap, cleavage, MW Aminoacid Protein ATG STOP poly A sites Dalton groups Remarks L1 52K 1219313329 42094 378 IIIa 13316 15043 63771 575 Protease cleavage site atamino acid 551 L2 15080 Penton base SA Penton base 15110 16657 56719 515no RGD 16196 poly A-site pVII 16679 16897  8562  72 Protease cleavagesites at amino acids 27, 40 mu 16929 17495 19787 188 Protease cleavagesites at amino (pX, 11K) acids 125, 144 17526 poly A-site L3 pVI 1755918230 23890 223 Protease cleavage sites at amino acids 28, 212 Hexon18289 21117 106704  942 18261 Hexon SA Protease 21134 21754 23763 206   21102 or Protease SA 21123  21767, L3 poly A-site 21836 L4    23608 or100K SA 23649 100K 23680 26634 109905  984 pVIII 27149 27886 26876 245Protease cleavage sites at amino acids 40, 115, 130, 141, 166 27920 LApoly A-site L5    28315 or fibre SA 28341 fibre 1 28114 30495 81526 79330509 [GCA]9 repeat 30511 fibre SA fibre 2 30536 31768 42939 410 31771L5 poly A-site VA RNA    39841 to 39751 E2 and IVa2 IVa2  6685  536650366 439 E2b pol 10268  6501 144984  1255  E2b pTP 11996 10269 66089575 Protease cleavage sites at amino acids 116, 141, 260, 264 DBP 2322421899 49272 441 23292 DBP cap site    21824 or DBP poly A site 21882

TABLE 2B Non-assigned open reading frame, larger than 99 amino acidgroups Right ORFs Left ORFs ATG STOP groups ATG STOP groups  794  1330178  5094  4462 210  1999  2829 276  4568  3549 339  3781  4095 104 3374  2892 160  5963  6373 136  1514  1191 107 33030 33476 148 3970539286 139 33169 33483 104 39256 38717 179 35629 36024 131 36144 35536202 37391 38239 282 35599 34238 453 40037 41002 321 33707 32892 27141002 41853 283 33058 32735 107 41958 42365 135 32429 31812 251

TABLE 3 Recombinant Adenovirus vaccines Pathogen Reference CommentsRespiratory Hsu et al., Glycoprotein F and G, inserted Syncytial Virus(1994) into the E3 region of Ad 4, 5 or 7 Hepatitis B Chengalvala etal., HBsAg, inserted into the E3 (1994) region of Ad 4 oder 7Pseudorabies Eloit et al., Pseudorabies Glycoprotein gp50, (1990)inserted into the E1 region of Ad 5 Herpes Simplex Zheng et al., Tandemrepeats of the epitope (1993) of gD Herpes Simplex Gallichan et al.,Glycoprotein B (1993). Rotavirus Both et al., Rotavirus antigen,inserted into (1993) the E3 region HIV Natuk et al., Ad4, 5 or 7, HIVenv, (1993) or gag-protease gene SIV Cheng et al., SIV Env Rev, insertedinto (1992) the E3 region of Ad 5 Rabies Kalicharran et al., Ad5 withrabies glycoprotein (1992) Rabies Charlton et al., Ad5 with rabiesglycoprotein (1992) Human Marshall et al., gB in E3 region of Ad5Cytomegalovirus (1990) Measles virus Fooks et al., N protein in AdE1Region (1995)

TABLE 4 Characteristics of the CELO Virus Genome. CoordinatesCharacteristics (Nucleotides) Category Left terminal  0-68 1 RepeatPackaging signal  70-200 1 unknown open   0-5365 3 reading frame L1 52K12193-13329 2 IIIa 13316-15043 2 L2 penton base SA 15080 2 penton base15110-16657 2 Poly A site 16196 2 pVII 16679-16897 2 mu 16929-17495 2(pX, 11K) Poly A site 17526 2 L3 pVI 17559-18230 2 Hexon SA 18261 2Hexon 18289-21117 2 Protease SA 21102 or 21123 2 Protease 21134-21754 2L3 Poly A site 21767, 21836 2 L4 100K SA 23608 or 23649 2 100K23680-26634 2 pVIII 27149-27886 2 LA Poly A site 27920 2 L5 fibre SA28315 oder 28341 2 or 3 fibre 1 28114-30495 2 or 3 Major Late 7350-76502 or 3 promoter (TATA box at 7488) Tripartite Leader  8651-8700, 8798-8857, 9682-9774 fibre SA 30511 2 fibre 2 30536-31768 2 L5 Poly Asite 31771 2 VA RNA 39841 to 39751 3 E2 and IVa2 IVa2 6685-5366 3 E2bpol 10268-6501  3 E2b pTP 11996-10269 3 DBP 23224-21899 3 DBP cap site23292 3 DBP Poly A site 21824 or 21882 3 right end open 31771 to 43804 3reading frame (right end) right terminal 43734-43804 1 repeat (roughlythe last 70 bp)

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54 1 43804 DNA CELO Virus gene (12193)..(15043) /gene L1 1 gatgatgtataataacctca aaaactaacg cagtcataac cggccataac cgcacggtgt 60 cactcgggtacaaattatga attcgatctt tggacttttc gacgcgccca gtgactgtac 120 tttattgcgccaattcacca cgcccgggag atttcgaaat tgctatttcc gtgcagttcc 180 gcattccgaagtacaattta accggtttta tgggtgttcg gtgtttttct agcttaatca 240 ttgtttttagacgacacagt gggtatctgt tttcgcttgg acttggctcc gctttgtgaa 300 aattcaactcgatccaacat tttccttatt gatggaaggc ttttattatt tgcacaacag 360 acatcgcgctatttacacag aacgcaaagt gctgtctttt ttattccttg ttccgggtac 420 atcttttattgctagtgcct cgcctatttt tagtcacgta tcttccttgt tctatagcta 480 tatattcacgcggttttcgg tctctcctca ctcggcagat gacttcggaa gagaagctgc 540 agagttcgtctccggagacc ggcctcgccg ctgtcgtcct gcaaagcccc cttgaggtac 600 gtgtgcctgccgttcttcct cctccagtgc gaattgacat ctaccgctac ccaggctttc 660 cgccaacggagaccatctgg cacggtctca tcacgcagac tgagttaaac caggctttgg 720 agagcatcgttgagcaattg tagtaagtgt cagtccctat ttttctgttt tttcttgtat 780 ttcctcttagacgatggacc cgttcggttc ttcttcagtc cctccgtgct ctacatcaga 840 ccttcccgaacccaagctct atttcgtccg cttgtcaccc catgcagtgc ctccagttag 900 ggctacgcacggagctgcag gatacgattt gtttagcgct tacgacatta aagtgcctgc 960 tcgcggtcgggcgctagttc ccacagattt agtttttcaa tttccgcccg gctgttacgg 1020 tcggattgctcctcgctcgg gcttggccgc caaatttttc attgacgtcg gagcgggtgt 1080 tatcgatcccgattaccgcg ggaacgttag cgtggttttg ttcaatttct ccgagagctc 1140 gttcaacatcaggcgaggcg atagggtagc acagcttatt ctggagcgta ttatggttcc 1200 ggagctgtcggaactgacgc agctaggcga gacagaccgc ggggcgtcgg gtttcgggtc 1260 cacaggtatgggtgctgtag accgcaatca gcgctctgtg ttggaatggc tgacccctgg 1320 ttcccgttgataggaccctt gcgacgaagt cgacttcgct gtacgcttgc aagcagattt 1380 tgagggggacgacgacacat acggacattg tctgtgcgaa ggcagcacca gcaagaggcc 1440 ctgctgtacgctctgtaaca gttactgcgt gcttctttag gtatgattgt gagcgtgtgg 1500 cagctcgcgaccatcgcgat tgagttttgc gataagtggg tggggaaata ctacagattc 1560 cgaccgtatcatgagagact tttgcttatg cagagtcggc aagctttgga aaggagcttg 1620 cgccgctgcgtaagtgaagt tggacctccg ccagagcctc tagaatagcg atggagtccg 1680 gcgcacgtggtgcttcctga ctttctgcac cattaccgtg gtgtttctgg ccttctttct 1740 gcagaaacttctcaactaca tagatttcag agatagcgac tgcacagaat gtttttttgt 1800 gtagttgacaggactatgga ccagacagca acccatacag ctttgattct tctgatcgtc 1860 ttgacggtgttcacgggcgc ggtggtagct ttgatgttgt atattgcgat aactggactt 1920 ccttgctctatgctttgctc tcaataaaga ttttcagaat ggtgattcta tggtattttg 1980 tcttttttctagacagtcat gtcgcgtgag tctgaacgtt actggacttt ggtgcacgct 2040 ctgattgatcggggtgtagt cagccgtgaa cagtggcaaa tggttgaccc tgcgcaatac 2100 cagttctaccaccgctccaa acagaggggt tttaaggtcc gtcacattct tcgtgatgtg 2160 attcgccacatgtgttggtc tcggactctg ttagattata tgtcctcggc ctcgacacct 2220 agtccggacgatgtattacg caatcccctg tatcagttgc tgttatgtaa tggatataac 2280 cccgctgttgtggggacagc gctgatccgg tgggcgggcc atcagagcaa ccgtaacact 2340 gtttggattcgaggcacccc tatgtccgga gctccgtact tggcacaggc tatcgcgtac 2400 tgctctcccctcgtagggag cgttgattgg cgcaacaagt ctaacccatt cgaagggtgt 2460 ccagatagtctggtgttttg gtgggacggc ggttatgttt atgattgttg tgtgggtctg 2520 gtgaagcaggtgttccgggg agaacatgtt attttgcctc ctgagggctt gcgtggcccc 2580 aacccgtgctctgaactctt caggacccca gtcttgatgt acagccaggc ggatatttgt 2640 atgactaggctgagatcagg ggaactaagt gcagagcatg cggtgggcct cagggattgt 2700 atgtacctgatccgtttgac agaagatttt gactgcgcgg gtggtatatc gtgtgcagat 2760 gtcaaacagtttgtggcgtg gagccgcgaa caccctgggg aggttcgcga gacccacgaa 2820 ctcaaataaaaattcgggac ttctgtgtac gttccttttc atgtttatta aacactgttc 2880 tttcgagtgagtcatatcac gtggaagtta attgcgactg ggagccgcag aagcaggtgg 2940 taaaagcaagctatgcaggg atagtttacg atgtcccttg gaagacagac atagagtgtt 3000 tgtccttccagtcgcgtgta ggcgccttgg cgccgcgcaa cggttactgc tgtatatatt 3060 tgttcgagggcagggttcaa gttgcataac ctgcagtgag tagcatatgt gtataagatg 3120 agattaagagggagttgggg ctggtggtcg tgttgagcaa cgaaattgac gaccgttttg 3180 gcccagtgagctgtaagcac tcggatgagg gataaacaaa agagggaacg gggtgtctcg 3240 cagctgcagatgtactggat agtccagtcg gtacatcgca tctcaataac tcttatccag 3300 ctgcagaatgacctgagctg gaggtcacac tcttcgtccg taatgcagtg gggcgagtgc 3360 ttgaaggggtacatctgtct tttaaggaga aagagtagga aatcgggatc tgtgattagg 3420 gtaatgcccacgcgcgtgaa caggggctcg atgtagatat gccaactgtg ttggggctcg 3480 tcctcatcgttgtcactatc ccaaacaagg tcgcacgact cgaatgtctg taaaacatca 3540 aaagtttattactgattttg aagaggggta cgtatacagg ggttacagag tttattatcg 3600 cgtttgcaatgcagtgtcat taagcaagca caagcggcag cattagcaac aaagtcgcgt 3660 agctctttgcgcgggtggta gcatggaggg gtcttggtgt ggtctcctgt gaggaagaag 3720 acgaccgtgttccgcgccgt gaactcgttg gcgagcgaga ggtccgcgca gtggattagc 3780 atgggggtcgaggggatgtg gaacgttttc ttattcagcc tgcaggtggc agcattgcct 3840 tccataaagtgcagcatcaa cgggtccggc ttctcgtcta cgaagggcag acagtataga 3900 gaggcgtggggtgcgatttc gcccagtgat agtatggagt tgattcggct gtcggagatc 3960 gcgagcgggaaacacgcgca taaggcatta aagagactct tggcgttgga aagtcttcct 4020 ccgcagagcacgagggtgtt tagttctcct cggagccatc ggaggatggc gttagctgcc 4080 acttttccctcgtagccttc ggcttccatc atctgatgga accagttgtc gcagacgttg 4140 tagaacgcagccttgagggt gtcgggctct tcggagggta actggttaat gaggctctgt 4200 ccgggtccgaaccgttcctt gagggcttcg agtacacgct ctcgttcgta ggtgggtatg 4260 aggttcttggacgggaagtt ccactggact tcgtgtgcta caccttcgac aaacaaccgt 4320 tcaaccaactgatccatggg ggacgtggac ggaaataagc agggtgaagg ggtgtctgga 4380 atgcaggatgctatttgctc ctcttcgcta cttaaagacg actgagactc gcgtcgcctc 4440 ttggtgcactgtgggagaga attatatgtc atgtgatgag tgacaagcat tgcatgggga 4500 ggtccacgagcgggaacaga gcattccttt gttctcgcat aggagagcgc gcaaggcgtc 4560 gttgtcattatctgcctgta attggtgtat gcgatgaatg tagcgggaga gctctcccag 4620 aaagaacccgcagccgttgg cgggttcgta gaacctaata atgatatgtt cgtcgggagc 4680 agtgggcagatgttcgggat gggggagctg atataagcgg acgaggcatt ttttctcact 4740 gatgtccacgagaccgtcgc gggtcattgt ggtgaatgac ctgcctttca gcagctggtt 4800 agcaacgggatctttgaacg tgttacaatg agctgtgcag gggaaataaa gcatcttgac 4860 taaatcttgctgtctggcgt actggccaaa gtcgaacgcg ttaatgttgg cagtgaggac 4920 aaattggaataatctgagga tggatgcagt gaatatatct gcggcagagg aaggttctcc 4980 tacgacatagagcgtgttag tataatggca caggcgacta atgctcatgg cagacatcca 5040 cagataaatggcgtagatgg ctaccggagc attgtaacct tcggcttcta gcatggctcg 5100 gagatctctttgtgaggaca gctcgaagcc ttgcagattg aaattgatcg tttgactgag 5160 cccgtagctgcagtataatt tgcgcgcttc ttccagaagc gcgggggcga ccgattcgaa 5220 tagttcagcatcttggggat accgagtgag ccaatctttg taggtaaaga tgttgtttcg 5280 ctggagatcgaatattagcc tgtgtgtgac taaatcgtcg tcgtcttctc ccgtgtggcg 5340 gttcctgagtctcttaacgc tatccttaag tttcctgaaa cgttcctggg ggagaaagtt 5400 tttcgagatcggttagtttg gggtttctct ctaactgctt tctatgtgtt tcgctaaatt 5460 tgatgatagatttggctgtt ttcaggaatc tctcctgaat gttaacattg agagggatga 5520 tcgagtactgctgatctata ctgcaccacc taaaggactc ggatactggg tccggagtgt 5580 acatgacccagctgaaccgc tggttctgct gcaggaagga aaagtaagct ttgagaagga 5640 caacgaggtccttcgagatg ttgtgtgcga acgcatagag gaacctagcg aactggaatt 5700 ggggaatatgacaggatagg atgtgcattt tcgcgttcac tttgagggtg ggaacgtttc 5760 ctatcgcggtgcgcggtgcc atgttgtgca agactacgaa aatgtagaag gctgtacagt 5820 gggcagagcgagcaaagagc ttagaaggaa gggcgtgaaa gaggacagag acgctggagc 5880 ctgaacagagcttatccatg cactcgtcca tgataatggc gacgggtccc cgcttggaga 5940 ctttcacgtaaatgttgtct ggatggtcga tgttgagatg ttcgggtgcg gtggcctcct 6000 cgtaagtcatctccataaat tcgggacgga acgtgcttgt cttaggggcg atggtgccgt 6060 cttccctgcagtcgaaattg gcctcgacca gctgcaggtt ccaggacgtc tgttcgatgg 6120 gtggaatcatgttcttttcc ggagtgatga agatgaccgt ttcggggatc gggtccaaca 6180 tgttgcacgagatgagcgcc cgcagcagat gcgacttgcc ggatccggtg ggtccgtaga 6240 tgaccccgatgatgggctgc ttgcccatgt tgatggacgg cagctgtccg tgttggaggt 6300 agcgactgtccatctgttcc tgggctttaa cttcttcgtg ggcttcgaga aacttctcat 6360 taacgccccctaggctgtag aactcgtcgt aggaggggaa gtgttgctcg cggaagagct 6420 gcggtgctaggtcgacagct ccgtcgtacc agctggtgac gcgctggtag aagtcccgcg 6480 aggcttcgtactcttcttcc tcatactccc aggctttccg cttcctggga gctatcatct 6540 gcgaagagtaggtcgtgaac ttgcccgcat tcctcttcgg ataggaacgc gtagggttcc 6600 catcgtaggggtgcgagggg gtcttcgtgc ccgacgattg ggacgggtcg tacgtctcct 6660 gtcgtgcggggatttgggtg ctcattgtcg taggggtaca ggtagtcccc gtgctcgtat 6720 agggtgaggtccttccacgg acgcagcact cgcgtgagct gctcgttgtg aatggtgaaa 6780 gggtcgtagcgactgacctt gttcagaagc gtggttttaa agatggttct ccgcgtgtgt 6840 agctctgggatgttgctctg cgctccgaat tgcacgtcct cgtgtctacg ccaacagcgc 6900 agcagcgtgtcgtagatgag ttcggactgc ctgtgtccct tcgatctgat tttcccgggt 6960 cctaccgtgcggcactgttc gttgacgcag attgagtttt tcagtccgta cagttttggc 7020 gctaggaagatggtttccga gctgtacgtg tcacttccgc aggctttgca cttgatgtcg 7080 caatcgcaggcccagtagag gccgggattt tctggatcga aagtcagtcg agtggattct 7140 gttttgattcggtgcgcgcc gcggcttttc atgcgatgat agcctgtttc tgtgacgaac 7200 aggctgtcggtatcgccata gaggctgcgc ggctcctccc ttcgcaggat gtgcactcct 7260 ctgtccggtccgtacaggat gtcacaccac tcgctgaaga aggccctcga ccagcccagc 7320 acgaagcaggcgatttgcgt ggcgtatctt ttgtttgcca cctgcttgtc caggctttcc 7380 agatggagcacggttagggc ttctggtgtg gcttcgagga gacgcatagg tttaaaccgg 7440 gtctcgttagcgcgagcgta gtgggcggag cttagctccc cctcgggtat ataagggccc 7500 gtcgcgagggtcgcctcgac ttccaggtct acggcgacga gaggatcgtc ttcggtaagt 7560 gcgtttttcggcttacgggc actctcgcga tcgctgtcgt ctccttcttc ttccccatcc 7620 tcttctgcttcgggctcttc ctgttcgggg tcgtctgcgt agcggaactg ttgtcgtaga 7680 ctctcctcactgaaggggtt aggcgcgttt tcgagggtga cttccgttcc gttgaacgag 7740 tcgtcattgagcagcgtgac gtgtttgacg atttcagtgc cttcgtagat gtttttctta 7800 tctgcttccgagaggtcctg ttcaaagatg atgcgcgtgg tgtccatgtt ggtggcaaac 7860 gcaccgtacagcgcgttgct cagcattttg gagatggatc gaatcacttc gttcttctcg 7920 cgatcggctttttctttggc gaggatgttt ttcgtgacgt agtcggcaca tagcgttttc 7980 cattccggaaaaacaatgtt catctcgtca tggaggacct ggactcgcca tccccggttg 8040 tgcagcgtgaggatatctat gacggtgacc acctcgtcgt agagagcctc gttggtccag 8100 accagtctgcctcccctccg ggagcagatg ggagggagtg ggtctaacat ttcgggcggg 8160 ggagggtaggcttctatttt caggatggaa ggcttgatac gcgcatcgaa gtagctcaga 8220 tgcgattcgttggtcagcag ccggttgagc tcctccacgt gctgcgcggt aaattttgga 8280 tctaggggcattccgtgggg catggggtgg gtgagggcgg aagcgtacat gccgcagatg 8340 tcaaagacgtagacgggttt caggtaaggt ccgagcacgt tggggtagca tcgtccgccg 8400 cggagcgcttggcgtatgta tttgaacatg gggcggtggg gggcgtagac ttcggccacg 8460 tagtcgggggagggttgttt tttctttttg gttcgacctt tctttttggg gggttcgggg 8520 acggagggagggcatgtcgc acgctgttcg cggacgtaat tggaaaaggt aagttgcttc 8580 caaaaggcatgagtgttgct ggggatggtg ggccgcacga agatgttaaa atggccttcc 8640 atccctagttctcgttggaa ataggcgtcg tagctgtcgt gtaacgtgtg ggccagcttt 8700 tgggtgacgcggacgtcctg catgcagtat tcgaggcacg cttggacgat gtcgtactgc 8760 tggcccgggtgttctttctg ccatagattc ttctgttcag cgatgacgga tgggtcttcc 8820 cagtacctttcgacaggaaa gccgtcggcg tccgcgtgaa agcgccccgt ggaaatgaat 8880 tcgttgatggcctcgtatgg gcaatgtccc ttgcagaggt ctagcgcgta ggctgccgcg 8940 gctttggagagtttggcccc gctggtgagc tgtagagtgt ctcgcaccat gaaccgcaca 9000 aataccgagcgcgcatcctg atgggacacg atcccgcgag accagcgttc tacgcgggag 9060 gcgtctttcttcacgtagtt ggggtttggc atgcggaaaa tgatatcatt gaacagaagg 9120 cgaccgacgcgaggcatgaa ggatcgatca catttgcacg cttccgggaa taggtccctg 9180 cgctcgacgagttccgtggc taagaggagt tcatcgaact tacatatgtt gtgacctagc 9240 actacgatgtctacggaata aaagttatcc gggagggaga ggggggaggt gggtttctcg 9300 aagagctcgtacggtatttt gtgaacggag ccgtactttc cgtccttgac tagctggtcg 9360 caataatctcggttggcagc cgcgtagcgg tcgactagat tttgggcaaa ttctatttgc 9420 agacgggacctgaagttgcg aaaccttctg gcaacctcgc ccggatggct gtctagccaa 9480 tagaagccttcgtcgagggc tttgagacgg tcgtcctgcc gtgctaagcg ttcggcgcgg 9540 gagaccagctgggggtctcc gctgagcatg aagcacaaca taaacggatg catgcgcttg 9600 cctttcttttcgaacacggt atacgtctcg atatcgtagg tgatgtacaa ctgacgtatg 9660 tgggggtgttgggctggaca ggagaagtgg acgtgctgcc acaaatcgct gcccgatccc 9720 tggacggcgtggtagtagaa ggcagagcgg cgttcgttgc acgagtgtcg tctgacccag 9780 tgtcggccgcaggtgggaca ctgttgaacc ggagtgcggc tggtgatcca gacccattct 9840 ccggtgacgtttttggcgat gagcatgggg ggaagggcgg gatgttcgga gatgtgcacg 9900 gtccgcaggcgcgctgtttt gcctttaaag ttgatgacgg tgacctgggc gggcttaaag 9960 tcggggagggagcgttcggg gtctcgggca tagtgcagat agtctattcg gtcgtagcct 10020 ctggctctcttagacagcag gaagcggtgg gtgcgtagga atttcttgag acctatgggg 10080 aatacagtgggttggaagcg gaagggctgt tcctcgatgt aatagacgtt tgtgcgtagg 10140 gggttgccccggaagctctt gaagtacttt cgggtctctt ccagccgttt agcggaaatg 10200 gttcggatgacgtgcgaatc ggggcccagc acgctgtccg tgaggggagg ccccgcgtct 10260 gcttccatttacagaggctg acctcgtcgc gccgccgctt cgatgtcttc gcggcggtgg 10320 cggagcacgcgtctgaggtt ggctttgatc tcctcgttgg tagcgatggc tacgatgcct 10380 ttaaatttgatgcggaaact gatgtcgatg ctatcgatca gctcttcgct gaggttgagc 10440 tgcttcagcacttcttcgat gtcaccggag cggtctctgt attgaatatc agagagaaac 10500 agttgttggtccgcatcgtc catgccttcg aattgacccg tccgttcgac catcataaga 10560 aaatcgcgtaatatacgttc ccacagggtt tcgaatatgg tggcggggtt ggattgctcg 10620 ctccatatgcgtttaaaaac ctgctgcgcg ttgacgtccc atcccacgac gagtacttgt 10680 aaggtcaggacgtcgacgta ccggcggaac tcgcggttgg cgatgaagtg gctgtacagg 10740 tagtagagtgtagaggcgat atgttcggct aagaagaagt acagcaccca cttgcgcagg 10800 aacgactctcccatgagtcc cgcgtcgcgc gcggtcagga gcatgcggta gaagtcgttg 10860 gcaaacctgaagagttcgtg tctccgggcg gccccgctga gctcgtcttg cagtgccccg 10920 atggcttcgagcgctgtgcg aatcacctcg tctaacagct cttcttcctc ctcttctggt 10980 tcttctacttccatggcggc ttcttctatt tcttcgggag ggggcgcggg ggaggggggt 11040 ctccgtcgccgccgcgtgac gcggggcagg cggtctacga aggcccgcac ggcacggggc 11100 ctaatgcggcgcgcttcgga cgcggtgatg gctctgccgt ggcggtctct agggcgcagg 11160 ccggtgcggtcggttacccg ccggctgcag agggtgatgg cgcctcctga cagacccgtt 11220 cctgctaaggaaacggcgtc gctcgctaga gtgctcatga aacatctcgc cattgtttcc 11280 gtaggttcctctacgtcccg tcttcctcga aacttgcgct cggcatcccg caccagttgc 11340 tgggtgtctagctccgcgaa ggcttccgcg aagtaggaga gccagtttgg ttcaaggaac 11400 acatcggatccaggtaagaa ccgatatctt tcttccgttt gaaatagatc atatgcgtag 11460 cagaatagatagtggcagag ggcgactctt agttggcgga tggcggcgag cagttcggcg 11520 tcggcggcagaggccgttcg catgaggacg ccttcttgca agccacccgc tccgttgccc 11580 gacagtaggctgtggtgttc ggcgtcgagc tgcggcaaca cttgtccgtg acggcctacg 11640 tcgattcccctacctcgcag atgcgcccgg cccatgtccg cggccacgcg gtccatgagt 11700 acggcgttgtgcatctgcgt gaacgtaccg tgaaagttgt cgagatcgag aaatcgcatg 11760 tactgccctacattgacggc gtaggagcag tcggtcagac aggtccaaaa gaggcgtctg 11820 ggtctttggggtgggctatc gtaacctatc tgcataaaaa cgcggttgtc gaaaaggtaa 11880 tcgttgagcgcgcggtgcat agcttggtac ccgaggagaa ggtgcggcgg cggcaatccg 11940 ttgtagggcggcgcggcgac gttcggcgat cgcggcgcga ggtctcggag ttgcattaaa 12000 cggtagtcgtacacccggct gacgagaaac acgcttcggg ggtggaccag ggctggttct 12060 tcccgaacgaggacatagtc agcggtgatg acgggttcgc agaagcggac ggtggctaga 12120 ctctgtccggtgagatccgc gaagactctg taagcctgaa attgagcccc tgacgttttt 12180 agaccgctcgtaatgcaccc cgtcctgcaa agcgttcgaa acgcgagcgt gagcgccgga 12240 ggaccccatcaacagcaacc gcagcagcaa cagcacggtg tgtcgtcggt ccgtcgtcct 12300 ccttcaccaccccgatatcc cgcacaacat gcctatcccg gcgcgggcgc gacacccacg 12360 gcaggacgaggcgatttcga cggcgcgctt gatcccgatg aaggaccggt cgcgtgcggg 12420 ctggcggccggggccggtgt ggacgaagtt agaatgaggg agcgggacgc cgcgcggcga 12480 gccacggtgcccgagatcaa tctttttaag gctcgacgtg acgtggtgcc caatggggat 12540 tacgagagggatctgatgta ccactcggga caggcaatcg atatcgatcg gcaacgtgtg 12600 ctcactccggaagactttaa ggggtccgag ccggctttca cgccggctgt caaccatatg 12660 cgcgcggccgagttgaagag ggcggctgag cagacggcat ttggggagga attgaggaat 12720 acctgccatcagacccgcat ccgcacggct ctgttaaggc ccgagatcgg agcgggaatc 12780 tactatctgtacgatttcgt ccagacttat ctggagcatc cggacggtcg ggtgaagctc 12840 aatcctcagctggtgttggt ggctcagcac gcgggcaata ctatgctggc gcagcgcttg 12900 tgggccatcgcagaggagaa gaatgcgtgg ttgagagatt tgatagagat ggcgtacatg 12960 atcgtgaacgatccgtacct caatacggag cagcagctgt cggccatctg cacgacggtg 13020 gtcgagttgagcatgaaata cgccaagttg gccgccaaga acggttaccc gtccatggcg 13080 cagatggctaaggcgcagga atttttctac cgggtcatgc aagcggtgct cgatttaggt 13140 gtccaagtgggggtgtataa caaccgacca gctcggtacc gtcagaagcg catgagcgag 13200 attccgcagatgactgacgc cgagtacatg ttcggtttga cccaggcgct ggagagcagg 13260 cctccgcagggcgaatcttt tgccgacgag gggccgtcag aatcggacga cgaggatgac 13320 ttcatctgatacgtttctgg ctcttgcgcc ctacgggcgt caggaggtgg cggacgccct 13380 cagttcgctcccagatggca aggacgcgcg gtcgctacgt catgcaccct acgcaaatcg 13440 cctcatcaaactccagagcg ccatggtgcc tccaaaagtg gacggtactt ccgagcgggt 13500 ggccgaaatcgtgaaagggc tagccgagca aggcgccatc taccccgatc agatgggcgc 13560 gatccactcagatttgctta atcgagctta cacgtggaat tccatggggg tgcaggagag 13620 catccaggcgctggtcaacg acgtgatcca cggacagaac cggacattgc aagacgagct 13680 tgcgcggacgaaagaaatag cgaatgcttc gctcttgacc caatttttcg attccctgta 13740 caaaacggtggatcgtgggc agcgaaattt tgagggcttt aagaaacttt tgcgtctttt 13800 cgtgaataacgtgccgaatg ccgaagtgta cgggtcttcg gggtccttta gcgtgcagat 13860 aaatcttggcggatctagtc aaaacatcaa tctgaccaat gcgtttgaga atttgaagcc 13920 gatatggggcgcacggtggg acgcggtgaa taatcctcgc atcggggcgc ttctgacacc 13980 caacactcgagcgttgttgt ttttcgtgag ctctttttac gactacgggg ctatggagcc 14040 cggtagttacttggacaata tcatgaggct gtacaaggag gctatcagag ccgatgtgga 14100 cgcggagggtgatgccatta tggagctcgg ggaggcgggc gcaaatctca acttgcggtt 14160 caacgattacaaggacacac taaactacct cctgcaaaat cgagaggttg tacccgacac 14220 ggctccgctggagctgagcg cggagcagga aatgctcttg aagtacctga tgaggcaact 14280 acgacaggctcttaaggacg gggtcccggc ggacatttct atcagtacca tgactcagta 14340 cctagatcctaggctgtatc agacgaacaa ggtgttcgtg gagaaattgc aaaactacct 14400 gttggcggctcaggcgcgca atcctgtgta ttaccgactg ttggtgctgg accccaactg 14460 gcggcctccggcaggcctat atacgggtaa ttacgtgata cccgaccgct acgactttga 14520 ggacgtgcagagcgagcttg aatacgcggg tccctccaga gacgagtatt tcgatgattc 14580 tttgttcgcaccaggtcctc agcgccgctt aaattcggcc gaggaggctc aattggagcg 14640 tgacatcgaatctttgaccg gccacattga cgaagagctg ggcgtccaat ctcaggctgg 14700 ctggctcgccgatcaccgcc tgcctgtcgc gttcgatggc gctctcagcc ttaccgaacg 14760 caacgcctacaacacgccgt tgccccccga ttcccacatg cgtagccgtt ctagctccgt 14820 cgctagcgatcttgggctat tgaacctatc tgggacgggg ggaccgggct ttttcgctag 14880 tctgcggccttccatcggca gccgtcaacc gaccggcacg gccgtgggcc tccgcccgac 14940 gacaccgtacagcggttcgg ggtgtatgag gggcaccggt ctggcgcgca aagttttaaa 15000 cccggccgcgtcgcgccggg ggcgcaagct acggttctac tgaaccctag actctgacga 15060 agaaacttaaaaacgcttac cgccatttcg ccgcgcagaa gttggaagga tgtaccggag 15120 cctgcgaccgccgacgtcga ttcctcctcc gcctccctct ggtccctcgc cttatccggc 15180 gatgatcaacggatatcccc cggatgtgcc ggtggggtca cctgccaacg gagatgcgga 15240 gctgttcgtgccgctccaga gggtgatgcc gcctacgggt ggacggaaca gcattagata 15300 ccggaattatgcgccgtgcc aaaacaccac caagtttttt tacgtagaca ataagctgag 15360 cgacttagacacctacaacg aggacgcgaa tcacagcaat tttaggacga cagtcattca 15420 taatcaggacttagacccgt caacggccgc cacagagacc attcagctcg acaataggtc 15480 gtgttggggcggagagctaa aaacagcggt gaaaaccaat tgcccgaaca tcagctcgtt 15540 tttccaaagtgatacagtgc gcgtgcgtct gatgagcaag cgcgatccgg ggggtaccga 15600 cccagacgcgggggtgaaca acccacccgg ggccgagtac aagtggtatg atctgaggat 15660 tcccgaaggtaactacgcgt tgaacgagat cattgacctt ttgaacgaag gcatcgtcca 15720 gctgtacctgcaggaggggc gccaaaacaa tgtgctcaag agcgatatcg gggttaagtt 15780 cgatacgcggtatctggatt tgctgaagga ccccgtgacg gggctggtga cgcccggcac 15840 ctacgtttacaaaggatacc atcccgacat catcctcctc cccggctgcg cggtcgactt 15900 tacgttcagcaggcttagtc ttctgctcgg tatcgcgaag cgcgagccct actcgaaggg 15960 gtttacgattacttacgaag atcttcaagg agggaacgtg cccgcgctgc tcgatctgtc 16020 ctccgtgcaggtagacgatc aagacgagga cgtgatcgtg gtggcagacg caaggcctct 16080 tttaaaagactccaagggcg tttcctataa cgtgatcacc actggcgtga ctcaaccgca 16140 aaccgcttatcggtcttggc tccttgccta ccacaccctg gactcccccg cgcgcaataa 16200 aacgttattgactgttccgg atatggcagg tggtatcggc gctatgtaca catcgatgcc 16260 ggacacgtttaccgcacctg ccggatttaa ggaagacaat acgaccaacc tttgtcctgt 16320 ggtggccatgaacctgttcc cgagtttcaa taaggtattt taccagggcg cgtccgccta 16380 cgtgcagcgcttagaaaatg ccacgcaatc cgcaacggcc gctttcaacc ggtttcccga 16440 aaacgaaattctaaagcagg ccccacccat gaatgtttcc tcggtgtgtg ataaccaacc 16500 cgccgtcgttcagcagggtg tgctaccgct gaagaattct ctgtctggcc tacagcgcgt 16560 gttgatcaccgacgaccggc gccgtcccat tccatacgtg tacaaaacca tcgccaccgt 16620 gcaaccgcgcgttttgagca gttcaaccct gcagtgagga gcggaaggat tttcaaacat 16680 gtccattctgatttcaccca gtgataacag aggttgggga gcaaacatgc gttaccgccg 16740 tagagcatccatgcgcgggg tcggtcgccg tcgtctcacc ctgaggcagc tattgggtct 16800 ggggtctcgccggagacggc gatccaggcc cacgaccgtc agtaaccgtt tggtggttgt 16860 gagcacccgccgccgctctt cccgaagacg ccgatgaagc aagcagctga tgagatgttc 16920 ttctgactatgtgtgccgtc gctatacaca ggagcgacgt cgttatgcct tccgttcttt 16980 tgaccggcgggcggaccgcc aagggcaaga agagagcctc tcgtcgtcga gtgaaagtgc 17040 ctaagttgcctaagggagcg cgccgaaagc gtgcgtcggt gacgccggtc cctaccgtag 17100 ctaccgcgaccgcttccgag cgcgcggctc tgacgaacct agccagacgg ctccagcgcg 17160 gcgactacgccgcttggagg cccgccgact acacgtcacc ggccgtttcc gaggcggctc 17220 gcgcagccgcctcgtccggc acccccgcga ccgcgaggga tctcgcgacg ggaaccctcg 17280 ctcgcgccgtgcccatgacg ggtaccggcg gaaggcggcg caagcgcacc gctacccgcc 17340 gccgatctctgaaggggggc ttcctgccgg ctctgatacc tatcattgcg gccgctatcg 17400 gcgccattccgggcatcgca ggcaccgccg tgggcatcgc caatctgaag gagcagcaga 17460 gacagtttaataagatttac ggggacaaaa agtgatgctg actggacgca ctaaaaggcc 17520 ctttcaataaacgcgttttt gtagaaccgg ctcgcgtcat ggactacgct gcgctatcac 17580 cgcatctcggtgggtgggcc ctgagagacc accacatcgg cgactctagc ttgagagggg 17640 gagccatcaactggggcaac ctcgggtcgc gcataaccag cgcgctgaac tccaccggtc 17700 gctggctgtataacaccggc aaccgcttcg tgcattcgaa cactttcaac cagattaaac 17760 aaggcatacaagacagcggg gtcatacgca acgtggctaa tttggccgga gagacgctgg 17820 gggccctgaccgacatcggc cggttgaagt tgcaacagga tctggagaag ctgcggcgta 17880 aagctttgggggaggaaggt ccagcgaccc aggccgaact gcaggctctc attcaggccc 17940 tgcaggcgcaagtggctgcc ggagagccgc ccgccgcacc cgcggcgccg gcgccggccc 18000 cgccgctcgtgcccaccact cgtcctattc ccgaaatggt aacggaggtt aagcctcccg 18060 ttacgtcttcggcgccagcc gtccccgtag acgtgccgac cacgctggaa atgcgacctc 18120 cgccgcccaagcgcaggcgc aagagggcac gaccgggaca atggagggca cgcttggaca 18180 gcctctcgggtaccggagta gcgaccgcca ctagacgtat gtgttactaa aattccgtcg 18240 ttccgctatgtctaattttt agctcaccgg ttgtctcccg aaggcgtcat gactgcgctt 18300 actcccgacctgaccacggc gacgccgcgg ctgcagtact ttcatatcgc gggccctggc 18360 acccgagagtatctatccga ggatctccag cagtttatct cggccacggg gagctacttt 18420 gacttgaaaaacaaattcag gcagacggtc gtagctccca ctcgcaatgt caccaccgaa 18480 aaggcacaacgtctgcagat cagattctac ccgatccaga cggatgacac gccaaacagc 18540 tatcgcgtgcgctacagcgt caacgttggg gacagctggg tgttggacat gggggcgacc 18600 tacttcgacataaagggtgt gctggaccgc ggaccttcct tcaagccgta cggcggaacg 18660 gcttataatccccttgcgcc aagagaagct attttcaaca cctgggtgga gagcactggt 18720 cctcagaccaatgtggtggg acagatgacc aacgtgtaca caaatcagac caggaacgac 18780 aagacggccacgcttcagca ggtcaatagc atctccgggg tggttcccaa cgtcaacctg 18840 ggacccggcctcagtcaact agcatcccgg gccgacgtgg ataatattgg cgtggtggga 18900 cgtttcgccaaggtagactc agcgggcgtg aagcaggcgt acggagccta tgtcaagccc 18960 gtgaaggacgacgggtctca gtctctgaac cagaccgcgt actggctgat ggacaacgga 19020 ggtaccaactatctgggtgc cctggctgtg gaagactaca ctcagaccct gagttacccc 19080 gataccgtgctcgtgacccc tcccaccgct taccagcaag tcaactccgg caccatgcgg 19140 gcatgcaggcccaactacat cggcttccga gacaacttta tcaacctact gtaccacgac 19200 tcgggcgtctgcagcggaac gctcaactcc gagcgctccg gcatgaacgt ggtcgtggaa 19260 ctccaggacagaaacacaga actgagttac cagtacatgc tggcggacat gatgtcccgt 19320 catcactacttcgcgctgtg gaaccaggcc gtcgaccagt acgaccacga cgtgcgcgtc 19380 ttcaacaacgacggctacga agagggcgtg cctacttacg ccttcctgcc cgacgggcac 19440 ggggcgggcgaagacaacgg tcccgacctc agcaatgtca aaatttacac caacggacag 19500 caagataagggcaacgtggt ggccggaacg gtttccacac agctcaattt cggtaccatt 19560 ccctcctacgagatcgacat tgctgctgcc accaggcgca acttcatcat gagcaacatt 19620 gccgactacctgcccgacaa atacaagttt agcattcgcg gtttcgaccc tgttacagac 19680 aacatcgaccctaccaccta cttttacatg aatcgcaggg ttcccttgac caacgtggta 19740 gacctgtttaccaacattgg tgccagatgg tccgtggacc agatggacaa cgtcaatccc 19800 ttcaaccaccaccgtaactg ggggttgaag tacaggtctc agctgctcgg aaacagcaga 19860 tactgccgtttccatattca ggtgccgcag aaatactttg ccatcaagaa tctgctcctg 19920 ttgcccggcacctacactta cgagtgggtc ctcagaaagg atcccaacat gattctgcag 19980 tccagccttggcaacgactt gcgcgcggac ggcgcgcaga tcgtgtatac cgaggtgaac 20040 cttatggccaatttcatgcc catggaccac aataccagca accagctgga gctgatgttg 20100 cgcaacgctaccaacgacca gaccttcgcg gactacttgg gcgccaagaa cgctctctac 20160 aacgttccggccggctccac gctgctgacc atcaatattc ccgccagaac atgggagggt 20220 atgcggggctggtcttttac ccgcctcaag gcctcggaga cgccccagct gggcgctcag 20280 tacgacgtcggtttcaagta ttcaggctcc attccctatt cggatggcac cttttacctg 20340 tcccacacgttccgcagtat gagcgtgttg tttgatacct ctatcaactg gcctggcaac 20400 gaccgtctgctcacacctaa cctgttcgag atcaagaggc cagtggccac cgacagcgaa 20460 ggcttcactatgtcgcagtg cgacatgacc aaggactggt tcctcgtgca gatggccacc 20520 aactacaactacgtgtacaa cggttatagg ttctggcctg acagacacta cttccactat 20580 gacttcctacgcaacttcga ccccatgtcg cgtcagggcc ccaacttcct ggacaccacg 20640 ctgtacgacctggtgtccag cactcccgtt gttaacgaca ccggctcaca gccgtctcag 20700 gacaacgtgcgtaacaactc cggctttatc gcccctcgca gctggcccgt atggaccgca 20760 cagcagggcgaagcctggcc cgctaactgg ccgtacccgc tgatcgggaa cgacgccatc 20820 agttccaaccaaaccgtcaa ctacaagaag ttcctgtgcg ataactacct ctggaccgtg 20880 ccgttcagctcggactttat gtatatggga gagctgaccg atctgggtca gaaccccatg 20940 tacacaaacaactcccatag catggttatc aactttgagt tggaccccat ggatgagaat 21000 acttacgtgtacatgctgta cggggtattt gataccgttc gcgtgaacca gcccgagcgt 21060 aacgtgctagccatggctta cttccgtacg cctttcgcca caggcaacgc tgtgtaaaaa 21120 aaagacggctgggatgtcgg gaaccaccga gacccaactg cgggacctgc tgtcctctat 21180 gcacctgcggcaccgcttcc tgggtgtttt tgacaaaagt ttcccaggat ttctcgatcc 21240 gcacgtgcccgcctcagcta tcgtcaacac cggctcccgg gcctccggag gtatgcactg 21300 gatcgggttcgcgttcgacc ctgccgcagg acgatgttac atgtttgacc ctttcgggtg 21360 gtcagaccagaagctgtggg agttatacag agtcaagtac aacgctttca tgcgtcggac 21420 cggcttacggcagcccgatc gctgttttac cctggtccgt tctaccgagg ccgtgcagtg 21480 cccctgctcggccgcttgtg ggctttttag tgcccttttt atcgtctctt tcgaccgtta 21540 ccggtcgaagcccatggatg gcaatcccgt gatcgacacc gtagtcggtg tgaagcacga 21600 aaatatgaattctccgccct accgcgacat cctgcaccgt aaccaagagc gcacctatta 21660 ctggtggaccaagaatagcg cctattttcg tgctcatcaa gaggaactcc gacgagaaac 21720 ggcccttaacgccctacctg aaaatcacgt ttaatgaccg actgtaaata aagaacgacg 21780 cacacacgtactgtacatat ttgtgaatag agcaaccgtt tattagataa acgtcaataa 21840 atgccgaccgatagaccgac aaggctcttc actggcttta tttaaagaaa caaaaggatt 21900 aagcgaacgggtcgtcactg gcgatgggcg agactggcgc caacacctcc gttttaaagg 21960 cgtacgactcgttccaacgg aactcaggca catgtgtggg ctctgaagaa cccatcacgg 22020 cagtaaacagctccgtagca aagacgtacg cgtagcgcag atccatggcc gacagacgcc 22080 aggcgcaggttttttcggtc ttcttcagac cgcggcctgc tccgcccgac gccgcctgcg 22140 ggttgcagcaggtgaacacc atggtatgcg ggtttttctt gtgagccttc atatcgggcc 22200 tgctctcgaccatgtcgcga gtaatgtcgt ctgtgccgtt gagcttataa ggagtcattt 22260 tacagaactgtctccctgaa atggctcgat cggaggcgta gttgcagttg caattggttg 22320 agatgaggacacattcctct gcccggcgct tgtccgcgtt ggggtaaagc gccttcgtcc 22380 agtctatgtcgtgacgcatc gcgctgaccg ccttggcggc gtcggaaaag accatggcgc 22440 aactgccgtgcgcgtgggga tgagggaagc cgctgtgctc ctgatccttg tagcacaccg 22500 cgttcgcgtcgaacctgagc accaccacct gtcgtccaaa ccggttcttc tcgattacgc 22560 cgttctgttcggccagagcc ctctttcccg cctcgctaga cgggttcaac tccacggtac 22620 gaggtttcgtcaccatgtcc acaccgtgca tgcatttcgg gaagggctcc tggagcgctg 22680 ggaaccagccatggcgccaa acgtgcgccc ctccgggcac gaacttgggc tccagacccg 22740 cgcggctgtagataacggct gccaggaacc gccctacctg agcgttgaaa gagtcgtagc 22800 tagaaaaggtcaggcgaaat tcgggatgct ttttgcgaac gtatgtaccc cccattttgg 22860 tccaaatggagtcgtcgggg cgcacgctgg ctccctgcca ctgtaggtcg agagcttcgc 22920 agatgctggcgacggtggcc atggcgcgtt gcgcgccgta gaccacgggg tctgacagag 22980 gggcctccggggattcctcg tcgctggcgt tttcttcgtc atcgacaacg gtttcccgcc 23040 ggcgggtaactcgccttacg ggggatgggg actcctcgcg gcggctgacc ttcttgcgag 23100 tcgcgcctcggcccggggcg accacttcca cttcttcctc ctcctcttcc atcatgactt 23160 ctgccgttctcttgacaggc ttggtgctgc gaaagccatg agctcttttc ggggttcttt 23220 ccatgacttctgcttcggtg acgggatctc gcgtttcaaa aagttcttgc tctccctcct 23280 cttcagagtcagggactact gccggagagg gtggaagcgt cttttgaagc ttcctgggac 23340 ctatagggtaaagttaacgc ccatcgtcag cgagaccacg cctcgctggc cgatgggatc 23400 acgagacacgataaaagacc gcgaccaaaa cactcttggg gctagtatcc ctacccgggt 23460 gcgagcgtggcagatcttcg ctcttctgct tctccagtgg attctcgggg tctttcggcc 23520 ccgtcggtctctggggtggg agaggcctgc tcctccctct gtttgacttg attaccgtcg 23580 acggcccgggctcttcgagg tccacgaagt ccgccacgtc ttcgtcgctg ctgatcgtct 23640 ctgggtgaagcgtttctgcc atcgtggctg tcatcgaaaa tggcagacaa gattacccga 23700 gaggaaaaaaccatagcgac gctggacctc gtgttacgcg tggtcgtcga tgctggtaac 23760 tgggacgtgttctcgaaacg tttggttcgc tacacacgcg aacagtacgg aatcgagctg 23820 cccgaagatatcggggactt accggacaca tctgaggtct cgaaagtgct gttgagtcat 23880 ttgggggaagacaaggcggt actgtccgcg taccgaatcg cggaactgac gcaaccttcc 23940 gaaatggaccgcgctaaggt cacagaggga ggcctggccg tacttaacgc gagtcgcgat 24000 gaaagcgaagctcagaaccc ctcgaacccc gaacccgaga gcatcgagag cgacgccgta 24060 gaggatctcggcgttgcagc agagagcgac cctagcgatg acgaacccga cccagaaccc 24120 gagtatgaccatcgagaggc ggatcatgac tctgatgcgg atagcggata ctattcggca 24180 gatgggggacgacctggaac accagtggac gaggagcccc aggacgattc tccctcttcc 24240 gaggagaccgcatccactgt catcgaagaa gcgcagacta gcgctagcaa cgattctcat 24300 gacgacgacactcaccgcga cgacggcagt gcttctgaag aggatctcga gcgggacgcc 24360 ctcgtggccccggccgatcc ttttcccaac ttgcggaagt gtttcgagcg ccaagccatg 24420 atgctgaccggggcgttaaa agacgccgcg gacacggctg atccgccaga aacgctctcc 24480 gtcgacagcgtgcaaaggca gctcgaacgc ttcgtcttta accccgaccg ccgcgtgccc 24540 gccgaacacttggaggtacg ctacaatttc taccctcctt tcctcacccc caaggccatc 24600 gcgagctatcacatctttgc cgtcaccgct tccatccctc taagctgcaa agccaaccgc 24660 agcggcagcgaccttctagc caaagcaaaa gagagcactt tcttcaaacg cttacctaaa 24720 tggcgtctcgggatagagat cgacgacggg ttgggaacgg aagtcacggc ggtaacagag 24780 ctggaagaggcaaaaatggt tccgttaaag gacgacgtgt ctcgtctgca gtgggcaaaa 24840 atgcgcggcgagcacattcg cttcttcagc tacccgtcgc tgcacatgcc tcccaaaatt 24900 tcccgcatgctgatggaaac gctgttgcaa ccgttcgcgg acgaaaacca aaaggcggaa 24960 gaggcacttccctgtctgtc ggacgaggaa gtgctggcca tcgtggaccc gacagggcgc 25020 ctccacggcgaggacgcgct caaggccgtg gaaaagcgga gggccgcggt cactatggcg 25080 gtacgctacaccgcgaccct cgaactcatg gaacgcgtgt tccgcgaacc gtctatggtc 25140 aaaaagatgcaggaggtcct ccaccatacc ttccaccacg gcttcgtcgc cctggtacgc 25200 gaaaccgcaaaagtcaacct gagcaactat gcgaccttcc atgggcttac ctacaacaac 25260 cccctgaacaactgcatcat gtccaagctc ctagaaggag cagacaagga ggactatgtg 25320 gtggactcgatctacctttt cttggtcctg acgtggcaaa cggctatggg tatgtggcag 25380 caggccatagacgatatgac tatccagatg tacaccgagg tctttaccaa gaataagtac 25440 aggctgtactcgctgcccaa cccgaccgcc atcggcaagg ccatcgtgga catcctcatg 25500 gactacgaccggctcaccga ggaaatgcgg aaagcgctgc ccaacttcac ctgtcagagc 25560 cagattactgccttccgcca ttttctactg gaacggtcca acatcccagc ggtcgccgcg 25620 cctttcatgccaagcgactt tgtgcctctg gcttacaagc agagccctcc cctcctctgg 25680 gaccaggtctatctgctgca gctggccttc tatctcacta agcacggagg ctacctgtgg 25740 gaagccccggaggaagaggc caacaacccg tccaaccgga cttactgtcc ttgcaatctc 25800 tgcagtccgcaccggatgcc aggtcacaat gcggcattgc acaacgagat tctggctatc 25860 ggaacgttcgagatccgcag tccggacggg aagaccttca agctcacgcc tgagctgtgg 25920 accaacgcatacctcgacaa atttgacgcc gaggacttcc acccgttcac ggtgttccac 25980 tatcccgagaacgcatcgcg gttcgcatcc actctaaaag catgcgtcac gcagagcccc 26040 gaaatcttgagcctgattcg ccagattcag gaatcgaggg aggagtttct gctcaccaag 26100 ggcaagggggtgtacaaaga cccgaacacc ggagaaacca tctccagaca gccccgggac 26160 actgcccgcgcgcagcacgc tggagacggt caagctctac cagcccctgg agcctatacc 26220 accggaggaaatagagcgga gacagcgcct gctggagctg tacggcttgc cccggactac 26280 caagacgggcagtttcctat cgcgaaagtc ggcccgcact accatggccc aaagaatgtt 26340 agacgagaagaccagggtta cagaggcggg cccggaggtg tacggggaga gcgcgaggtc 26400 gtcctttcacgaagagcagg aggaagacgt ttcggacgga gaaacactag gcagtcagga 26460 tacaacgaacgggctaaccg atatttcgga agaggaggag gaggatctgt tcgagggcaa 26520 caaggagaacatcccaccac ctcgccgtcc gcctcggaac cgccggctcc gagccgcata 26580 ctcgctcgaggaacccctcc ttcccccgag cgccgcgacc gacaagaaga gtaagaaagt 26640 cccaaaaaggcgaggtaaat atcgcagctg ggctaagcac cgcgtggcga tatgccaggc 26700 acttcgcgatgcggtctttg accgcaaaaa ggcgggcgaa atcctcaagc ggggtcaccg 26760 gctcttcgtgcccgctactg tcataggcta ctatgctcgc aaactctctc cctcatttct 26820 cgctcctctctccagccaca ccgcacccct cctcccacca aaaaaacacc ggcgctaagg 26880 ctgtgcgtctgcgccaagat ccggtgccgc agcacatcgc ggacctcaga ggggaaatac 26940 tcgacatcctgttggaaatc gagtcgtacg cccgccgccg tcccgaccgc cacgtgtcca 27000 ttcgcaacagaacgcgcgaa agcatcaccc gaaaactgca ttacgagaaa aatgaagata 27060 agcttacccgtatgaagagc gatgctatca agttgctcgc tctctggcag accgtttaac 27120 tcgtgttcctttatagccct tcggaaccat gaacctgatg aacgccacac ccaccgaata 27180 cgtatggaagtacaacccag tctccggcat tcccgccggc gcgcaacaga attacggcgc 27240 cactatagactgggtgttgc caggaggaac cggtttcgca atagcaacca acgacattcg 27300 aagacaaacccttaacccgg ccgtgacccg tgcaattacc gcgcgttttg aagctgagtc 27360 agaccagcaaccgtacgcta gccctcacga gaccaatgtt atcgcggcca atgtcctcga 27420 ctcgggttatcccaaatccg gtctctaccc attagagctc agcggcaatc agcgcgtaca 27480 gctggcaggcggcctaatgg taggtcgcac tgagggcagg atgcaattag cgggcggttt 27540 aacagaaggaagagtgcaac tttctggagg tttccacgga cggccgttgg ttagagggcg 27600 gagcagaagaccgcccagat ggtgcggcgc cgaactgact gggaacggac tgcccgagca 27660 agccgaagtcacttctgaca cttacaagta cttcctgaga acacagggtc ccagccaagt 27720 ggttgaagagcccggcgtct tttcgcaaag acaatttatg actaccttcc tcccctccgt 27780 tgtccctcatcccttcgaca gcaccaaccc cggcgatttc cccgcgcagt acagtgccat 27840 ctacaaaggccgcacggcct tcgaagacac cttttgggac tggtgaagcg caccttttgt 27900 tggcgatgctccgtttcgca ataaatttct tccaattctc tgtcgttaaa cggctcccgt 27960 ctggtcactgtcacgcgctc gccgccctcg ctcgtcaccc gcgcgcggta ccgtcgcctc 28020 agccagaatacaaaaccggg gttcaggggt tcgtcgaacc gtaccacagc ctggtcgttt 28080 aatctcaaccaatattttct agggttcgac atcatgaacg aggaggttcc cctaaagcgt 28140 gtcagccctgacgaaaccga gacggttccc aaaaaaccgc gaaccgacgt tcgcgacacc 28200 gtcagggccggcactgacga cacggtagat ctcgtgtacc ctttttggtg gaatctcgga 28260 acgggagggggcggaggagg aggaggcggg ggcggcggca gtggaacctc tctccagccc 28320 aatgacccgctttacgccgc cagcgggacc atcaacctac gcatgacatc cccgctaacg 28380 ttgtcacaacgagccttggc tctcaaaacg gacagcaccc tcaccctcaa cacgcaaggc 28440 cagctgggcgtcagcctcac ccccggagac gggctcgtcc tcaacaccaa cgggctcagc 28500 atcaacgcagacccgcaaac cctcgcattc aacaacagcg gggcgctcga agtcaaccta 28560 gaccccgacggaccctggtc taaaaccgcc acggggatcg atctgcgtct agatccgacg 28620 acgctcgaagtagacaattg ggaactagga gtcaagctcg atcccgacga agccatcgat 28680 tccgggcccgacggtctctg cctcaacctg gacgagactc tgctgctcgc caccaacagc 28740 acatccggcaaaacggagct cggggtacac ctcaacacca gcggtcccat tactgcggac 28800 gaccagggcatcgacctgga cgtcgatccc aacaccatgc aggtgaacac aggaccttcc 28860 ggaggcatgctggccgtcaa actcaaatct ggcggcgggc tcaccgctga ccccgacggt 28920 atctcggtcacggccaccgt cgcgcctccg tccatcagtg cgacagctcc tctcacctac 28980 accagcggcaccattgcact cactacggat acgcaaacga tgcaagtcaa cagcaaccaa 29040 ctggccgtgaagctcaaaac gggaggcggt ctgacggctg acgcggacgg aatctccgtt 29100 tcggttgcaccgaccccgac gatcagcgct tctcccccgc taacctacac caacgggcaa 29160 atagggctctctatcggaga ccaaagcctc caagtcagct ctggacagct ccaagtcaaa 29220 ctgaaaagccagggcggtat tcaacagagc acgcaggggc tgggagtggc ggttgatcaa 29280 acccttaagattgtgtctaa cacgctcgag gtcaacacgg acccgagcgg acccctcacc 29340 agcggcaacaacggtctcag cttagcggcc gtcacacccc tagcagtgtc ttccgccggc 29400 gtcaccctgaactatcagtc ccctcttaca gtcacgagta actctctcgg gctctccata 29460 gccgcgccactccaggcggg tgcgcaaggc ttgacggtaa acacgatgga acccttgagc 29520 gcctcggcgcagggcatcca gctgcactac ggacagggat ttcaggtcgt cgcgggcacg 29580 ctgcagctgctcactaatcc ccccatcgtt gtctcatccc gcgggttcac cttactctac 29640 actcccgccttcacggtgag caacaatatg ttggggttga atgtagacgg cactgactgc 29700 gtggctatcagttcagccgg cctacagatc cgtaaggaag ccccgctgta cgtgacctcg 29760 ggaagcactccagcattagc ccttaagtac agctccgact ttaccattac caatggtgcg 29820 ctcgcgttagcgaacagcgg cggaggagga agttccacac ccgaggtggc cacctatcac 29880 tgcggggataacctactcga gtcctacgac atcttcgcct ctctacccaa caccaacgcg 29940 gctaaggtggcggcttactg ccgtttagct gctgcaggtg gcgtggtcag cgggaccatt 30000 caagtgacaagctatgccgg acgatggcct aaagtgggca acagcgttac ggacggcatc 30060 aaatttgccatcgtcgtgtc tccccccatg gacaaagacc cacgatcgaa cctcagtcag 30120 tggctgggtgccaccgtatt ccctgcgggc gcgactactg ctctcttctc acccaacccg 30180 tacggctccctcaacaccat caccacactg ccatccatcg cctcggactg gtacgtgccc 30240 gagtccaacctggtcacgta taccaagatc cattttaaac caacggggtc gcagcagctg 30300 cagctcgcgagcggagaact cgttgttgca gcggcgaaat cgcccgtgca gacgacgaaa 30360 tacgaattgatctatctggg atttacgctt aagcagaact cctcgggtac caacttcttc 30420 gatcccaatgcctcctccga tctatccttt ctgacaccac cgattccgtt tacttatctg 30480 gggtactatcaatgaacttg ttaactcctg cagcagcagc agcagcagca gcagcatggc 30540 tgaccagaaaaggaagctgg cggatccgga tgccgaggct ccgacgggca agatggcccg 30600 cgcgggtccgggagaactgg acctcgtcta ccctttctgg taccaagtag ccgctcccac 30660 ggaaatcacacctccgttct tggacccgaa cggtcccctg tactccacgg acggcttgtt 30720 gaacgtcaggctcacggcac ccctcgttat catccgtcaa tctaacggca acgcgatcgg 30780 ggtcaagaccgacggaagca ttaccgtcaa tgcggacggc gcgctgcaga tcggaatcag 30840 cacggccggacctctcacca ctaccgccaa cggcatcgat cttaatatcg atcccaaaac 30900 cctggtcgttgacggtagca gcggcaagaa cgtcttggga gtgcttctga aaggacaggg 30960 ggcgctacagagcagcgcgc aaggcatagg cgttgccgtc gacgagtctc tacaaatcgt 31020 cgataacaccttggaagtga aggtagatgc tgcaggtccg ctcgccgtca cagcagccgg 31080 cgtagggttgcagtacgaca acacccaatt taaagtcacg aatgggactt tgcaactgta 31140 ccaagcgcccactagcagcg tggccgcatt tacatccggg acgatcggct tgtcctcccc 31200 tacgggcaattttgtgagct ctagcaacaa cccgtttaac gggagctact tcctgcagca 31260 gatcaataccatgggcatgc tgactacctc gctctacgtc aaagtcgaca caaccaccat 31320 gggtacgcgtcccacgggcg cggtaaacga gaacgcgcga tactttaccg tctgggtgag 31380 ctccttcctcacgcagtgca acccctcgaa catcggtcaa gggaccctag agccaagcaa 31440 catcagtatgacctcttttg aacccgccag aaaccccatc tcacctcccg tgttcaatat 31500 gaaccaaaacataccctact acgcttcccg attcggggta ctggagtctt accggcctat 31560 cttcaccggctcgctcaaca cgggaagtat cgacgtacgg atgcaagtga cgcccgtcct 31620 cgccaccaacaacacgacct acaatctcat cgcctttacc ttccaatgcg ccagtgccgg 31680 actgttcaatcccaccgtga acggcaccgt ggccatcgga ccggtggtgc atacctgtcc 31740 cgctgcccgcgcccccgtta cggtctgaac aataaagaca aggtgaacca tttatacagt 31800 ctcacgtctctttattgcat acgctccgct aaatgtttcc attcgctcat ttgccagtaa 31860 tacagcagattcgcaaactc actgaaccaa tcttctgtat aaaaatgtac gcgctgcgtg 31920 tccaaatcaacatcaatttt cctcatatac agacaggggc tgccacccgc ctcccccaag 31980 cgcgacaccgcaattaggaa tggtagcctg ctgtgcaggt ccacgtgaat taacatcccg 32040 cacacgttcccgatcggtcg ctgcataaat actggagaga aatcgctaaa ccccggtgac 32100 gcccacatagccacgaagta cacccctgcc acattcaagt catcctccaa cctggcccaa 32160 acataagtggccaaatcgga aggagccagg tggcaagccg ataaccccat acgatgcaaa 32220 ggtaacccgtggcaagcgca tcccccgaaa tgaagttcga aagaatcgta acacagtagc 32280 tgataggcatgaagcggcgt cggcatctga agaccgtcat catcttcgtc gtcttccatg 32340 tcatccccaacttcctcctc gcgctccgct tcctgttggc ggcgctgctg gtgctgcagc 32400 accatctccaggatctgctc gtcgttcatc ttaatccgga attatcgcgt acggatgttc 32460 ctcgtcgtccgaactgacaa cagaaggcgg aggagctgtc agtggtgctg tagaggctaa 32520 cgatgctgcagcaccggtct cttgcaattc gaaataccaa gggttgctac tgacggtcca 32580 gttcccgccccgtgaaccag gccagcggga aatcggtgca ggtaggggat ccggtgaagg 32640 agaccgggaatggagggaag gaactgcgag atccttatcc actcgataca aaccgtataa 32700 cagggagcccaacgccaggt acaccaggaa cgtactacaa acgaacacgc tgattacaaa 32760 gtttaacgaagacagatggt tctgtaggaa caggaagctg cacaggatga tgctgctgta 32820 ggacagggcgaccaggaggg ccaagaactc gcgccaatag cgtccacaac actgcaaaat 32880 caaacacgtaattagctata cggacgttca ccagcgactc tcgcgcgtcg ttccataaac 32940 acattgcgcagataagccaa ctgagcagaa cagaacagag agagaggttg ccgcgtcgaa 33000 cactgtttgcactgtccgaa acactcggga tgagactccc cgtacttccc gtgcacatga 33060 aatacccactcttcgacgtt agcgtaggac aaccgacggt aaccggggaa gtaacacagt 33120 ccctgcgacacgatcggcca cagttccggc gacaccatca cgcggagcat gcttctcagg 33180 cagacgggttgggtcacggc gctgctgcga gaaatagttt ccaccatgat ggtggccgtc 33240 acggtcacgcgacacgcatt catgagaaca accggagacc gcacaaaagg aacagacgaa 33300 ggcacttgcgaaaaggacac ctcaaagctc atcgagcgga gagccatctt tacggatatc 33360 ttctccgcaatcagaaagcc tgtggtgaaa aacttaaaat ctgtcttcct gcgagcaagc 33420 atccacggttccaagtcgta cttcatccca ggtgtaataa aaagcaacct acgtgagagg 33480 tagtgcagcagggcggtctt ctctgcccgg ttcaggtgaa gggcactcac aatccggact 33540 atgcaattcatgagtacgta gtctcgccgt ttgaaacaca caaactttgc gctgcgtacc 33600 gtcactagcaccgtgacaga actatgcaat cgcctcatca gatcattatc gaaacaccgc 33660 aagctagccacggctctatt tatgcggtac tcgttcagtc tctccatttc ctcctgtcga 33720 caagttggatcgtgacgtag gagaaaacta aaccatatta ctcctacttc gttatgaaag 33780 ccacaagctctgctgacggt taaagactcc ttaagaaaga aaaggtagta cagtcaagct 33840 gacccatacaggtgaacccg ccccaagtca cgtaagtcaa ctcaccgaaa gaggacacag 33900 agccatatccgctgcttcaa agctttattg acgggtctaa aggcgtaaag aaaagaagaa 33960 tttaccgttctgcatctcaa accccaccac cacgcgaaaa agtccgaacg atgctgcagc 34020 accgttcacgcaaaagtccc ggacgcgcac aaataaaccc ttaatcccga taacggtgct 34080 gcagcaccgtcacgctgctg cagcatcgtc agacgtttat gacatgcagc cgattccgtg 34140 cggatttatggtcccataac ggttccaggt cctttcgttg ctgcagcacc gtttcacgta 34200 aagaagctgtacaggtcaaa ctggtccgga ttactgatta ttcgggggag agccacgtga 34260 cgtagactcgaacgacgtcc acttccgata caaaccacat ctctctggac acaggcttgt 34320 ccgccttgagccaaaccatg tgattcttcc ggtccgttct gacgtcaatg ccgacacgcc 34380 tcttggtgtttgaacaggca tcccagtacg tagccaggac cactcggtga cgtcgaggtt 34440 gaggtttaaaggtcactacg gcctgtaacc cggtactcca gggccctaaa ctaacatatt 34500 ctccggccctgcccactaca ttcgggtgat caaatatgac ataatcctta aacaatttgg 34560 ggaacttcaaacagccacat ttgggcggga caggaagatg gtgcgcagaa acattgatat 34620 gagagcgccatctagggaca tcaaagcggt gcccgcctgg atggcaatcg tacttcttag 34680 ttccggtaaagtaataggtg tgagtccgga aacacgtaaa ctccgtcact tcctgtgtcg 34740 tcattgccctcgcccctagt gacgtcagag tgccacgccc cttgtacagt ctaataaatt 34800 ttaatacacccccgccccta gcatataaaa caatgggagc ctcgcccaca ttcctatccc 34860 taataaaataccatctgacc gaatacccgt gttccatccc tattgtttta gtataataag 34920 ggtcataagtccacaactcc gcggcattgc cctctgtcac caccaacagc aaataggaag 34980 atgccatgtcatcctctcgt aaaagcatcc tccaatcagc tacctcttcc gtgtagtact 35040 gagttggctgactgtaatca cgccccgtga cgtaggctga ccacgcggaa ggaacacttc 35100 cgtgcatgctcagtagctgg tcagcctggt gagtatccag ggccttcata aaggtcaaag 35160 gcgccataatgtgataacac agtccatccg atcggaggaa atcaaaggga atatgtacat 35220 cttcacaatggcgcctccca gaataagacc atgcacagat ttgacctttc caccaagcac 35280 gtgactcgcaagcctcatgt ttttgaccag tcagatcgct ccgtatatac tcgtctccta 35340 ttggtcgatcaaaaccgtac gaaccaatac tagacgcaat caccactacg taatccgcgt 35400 catccctagagataacacta tccgcatccc tattggctga ccaatgacca ccggaagaca 35460 gcaaaaggtttaaccctttt gtgtgtaagt ccatcctata accctggaaa ctttccaatg 35520 ggggatctagcgccactatg cggccaacct tttttgaccc tctgtccgga ctagaagttg 35580 gcgggacaaagccgcgcata cagtgccccc tagcgacatc cctatgcaat gaattcgatg 35640 gtccttgaactccgtaaaaa aatgagcagt ggtcctgact gcgtaatagg ccggccccct 35700 cacatcctgcccccacaaaa gggcgtctac cttcttacaa atatctctca gctgattggt 35760 ccagtccaacagaatgaccg gggactctgg cgtcataatg gtatgcatac gcaaaatctt 35820 tctcatcatttcactggtcc atttatatgt gccgtcatag cgcgccctat taataagcgg 35880 acacacatcgggatacatgt cctgaaccag aataatgagc tccccgctat ctttaccatc 35940 caataccccgagccgccgca tttgactgac aacccagggg ccgtccgaaa aagtcaaaaa 36000 agtctcattccaccatacaa ttaacttggg ccacgaagga aaatccggcg aataggtgcc 36060 catcaagcgcctgacgtcag ccttaggata tggcggatcc catctggaat ccgacccatt 36120 aaagcacgaagatagggcag acatcggcca atggccagga gaatgggtag aattaataag 36180 gactccgcctccatttccga gcttttaaaa aaaagagaaa atggaaatca gccaagagac 36240 caccaccccgtgattggatg attggtcatc agaagatcga taagggaatt tattttctgg 36300 gagccccccccccccctact cctatttaaa aaataaccct ttcctcacca agctcagaag 36360 acagaggaggagagtagagc gccgctcaga ggtcatccgc cgagagaaaa tcccgcgcag 36420 agaacagagctctcaggtag gggtctggag ctctctggaa aaatcgcggg ctcttataca 36480 cttactctccgcccattcga aagccgcgcc tgactagagt acacactata aattccattc 36540 cggtgacttactactaggcg ctggccactt atcaaaagaa acagttctaa gaataggaca 36600 aagtccaaccgcaataaaac acccttgtca aacatgataa gagtgttctc gagaaggtac 36660 tggaaaagcaaacagtccaa ctcccaagtt aaatattacg caaagaggcg taacgagaaa 36720 agactagaaagtgtaaacac acctctccta gttatatata aacccagcgg ggcagtccct 36780 agaagaacactacctcaatc cagttacaca ttaacccggg aacctattat tgattaacta 36840 gacagtacttcctcattttc tactggaact ttccactgcc ctccggggat tttccattgg 36900 caatcattaacttgactttg tactttatgt ttactctcca tagcaacgca ccttatatgg 36960 aaaatatgctcctccccgga ccgcccatcg taccacctga gcaggtaggc tgtacctttt 37020 cctattggcccattatgagc tcacctggtt aatcatatac ccgctccgcc tatataggta 37080 gcataccgggacaggttccc tcacagtcta ttgcagactg ccgaagagag aggagctccg 37140 cataggactgggaccagaac cccgagactc tgccggtaat attttaattt catttaatcg 37200 aatcaaataaatcaaaaatc aactcaaacc catgattctc aatggaaatt tcttgtgatt 37260 ttctttcgcgcgcgaccacc ccctatggca cccccctgta cacccccctg tacacccccc 37320 tgtacaagggaacctacccc cctgtacagc gaccaccccc catggacacc cccctgtaca 37380 ttctacaggtatggcccgca acccattccg catgttccct ggggaccttc catactacat 37440 ggggaccatttcctttactt cggtggtccc tgtggaccct agccagcgga atcccaccac 37500 tagccttagagaaatggtga ccaccggcct gatttttaac cctaacctga ccggcgagca 37560 actgcgggaatactcattca gccccctagt gtccatgggg agaaaggcaa tcttcgcaga 37620 ctacgagggtccccagcgca ttatccacgt taccattagg gggcgctccg cggaacccaa 37680 gacccccagtgaggccctca ttatgatgga gaaggcggtc cgtggcgcgt tcgcggttcc 37740 tgattgggtggccagggaat actcggatcc cctcccccac ggcataaccc acgtggggga 37800 cctgggcttccccattggtt ccgtgcatgc cctgaagatg gcgctagaca cactgaagat 37860 ccatgtccctcgcggagtgg gggtccctgg ctatgagggt ctctgtggga ccaccaccat 37920 caaagccccccgacaatatc ggctcctgac cactggagtt ttcaccaaaa aagatctgaa 37980 aagaacacttccagaaccat tcttcagccg attttttaac caaactcccg aagtttgtgc 38040 catcaagactggcaaaaatc cgttttctac agaaatttgg tgtatgactc tcggcgggga 38100 tagccccgcccccgagagaa atgaacccag aaatccccat tctctccaag attgggcaag 38160 actgggtgtcatggaaacct gcctacgtat gagtaggcgg ggactcgggt ctcggcacca 38220 cccctaccattctctgtaac caatccctga ataaagattt gcataacaga actttgactc 38280 ctccttttatgtgggtgggg taatgggcgg cacttggggg taatggcggt tcctattgga 38340 tgggtaacaccgactccgcc ctacaaagtt aatgattgat ttttcggact tagaaaaatt 38400 tcgactgtcacctggatgtt tttccccact taacctctag ggggagatag atcgcgtcca 38460 aggggaggagctcaataccg gaccgcctat taggtgtggc ttcgggctcc gcctagtggg 38520 aggagacaggaaaaccacgc ctagtgacgc tgggtcaaag tccaagggga gtggtttatg 38580 cgcaccgccttggggcgtgg tttgggcggc gcaaggtaac ccttggactg ggaggagact 38640 tctgtcccttgggcgtgtca aacaggtaaa ccccacccgc gcgattaatg attaattttt 38700 cggacttagaaaattttcaa cctgatactt tattttcaag cttttcccgc cgacgggcaa 38760 gcctcctatctctccgtcta tgactccaca gagcctcatc tgaatatgta aatgtgctga 38820 accgcaaccccgtagaccgc gcccacccca gcatcaaagg taacgccccc gatgccacaa 38880 tgtaattacccactgttaaa ttaggatcct tacaccaatc atttctgtac aatttaaacc 38940 accgcccacgcgggactttc ccgtggtggt agaaaaaggt tttgaaaaac gcgcgcatta 39000 ttttcgtggcttcattaata gcggacatgc gcagatccag aaaggtcaga cacaccacca 39060 cggtcacatgacatttgcat ggagacaggg attggatacc gacacaatac gccatcggat 39120 actgaatgtccacattggtc cgtgcatata cagtgtgcca cctcctcttg accgcagcca 39180 cgaatccccagaagagttct tcccgccaca aaatcgaaac cggggcggcg gccccaaagc 39240 acaaatacaaaggcatcctc ctgaggctct agaaaaaaca actcattaac aggcatcccg 39300 ctcataggtacattcgtgta aacagggctg catgccaacc aatgccccgc gttttacaaa 39360 gtgacgggccaccctattgg cggagggggt ccacgtattg cgcaccgcgt aaatagaagc 39420 cacccctcgcggaacctgtg tacattcaaa tctcctccaa atacattcgc gcagtaaagc 39480 caccgcccttttcaagaaag tccaatcaac cttatgcgtg ggcaaaaaaa tagaagctga 39540 atatacccccgcaaactcct ccaatcggaa caggtaatct acactatagt gggacagcat 39600 ctcaacagttaaactttccc aggcatttat caccgtcaat ttcagatcat ggaatacggc 39660 caagttaggctccatcaagg tcacgcggag gtggaagtaa tacatcccga aataccctgt 39720 taaaaaaaatagaaaaatga actaaccgac aataagatcg gcagtaccca gtttcgatct 39780 ggggacctccggagtgcaag tccgacgctc ttacggctga gctacactgt cgatcttgat 39840 ccgctagggtacgcagtccg gagaagaaat atactaagtg agacccggtc ctatatatac 39900 aggttggttcaaaggaacct ttgtacccat taaaacaggt gcgtgactgt agaagccaca 39960 cccctacctgtaccgataag gcacaccctg agcaaacaaa ccataaaggt atacttcctt 40020 attcagacaggtataaatgg aacctccgca caacagtccg gtaccatttt ccatcgcgaa 40080 aatgggcaaccctactctgc tccttctttc aggtctcctt tctctgaccc aggccatttc 40140 catcggagaacacgaaaaca aaacccggca tgtgattgta tggcggcact cctcctccca 40200 ccaatgctctgattggagaa cagtcacgga atggttcccg ccccaaaaag gcaacccggt 40260 gagaccaccctacacccagc gggtttccct ggatacggca aacaataccc tcacggtaaa 40320 acccttcgagacaaacaacg ggtgttggga aactacgtca caaggcatta accatccacc 40380 aaccaccattcagtaccggg tatggaacat caccaccacg cccaccatac agacaatcaa 40440 cattaccaaaataactgttc gggaggggga ggactttacc ttatacggac ctgtgtccga 40500 aaccatgagtattatcgaat gggaattcat caaggatgtc acgccccagt tcatcctcca 40560 atactatctctccattaact ctactattgt gtacgcaagc taccaaggga gagttacctt 40620 taaccccggtaaaaacacac taaccttaaa aggcgcgaag accaccgaca gcggcaccta 40680 caagtccacggtgaacctcg accaggtatc cgtccacaac ttccgagtag gagtcacgcc 40740 catcgagaaaaaagaagaag ctaccgcaga gacacctgcc agcaagccca cgcccatacc 40800 acgtgtccgagcggatgctc gaagtactgc cctatgggtt ggacttgccc tttgcatcct 40860 gactgttatacccgccctta ttgggtggta cttcagagat aggctctgtg ttcccgatcc 40920 aatcattgaactggaaatcc ccggacaacc ccatgtaaca atacacatat tgaaaggtcc 40980 cgatgatgattgcgaaactt aatgattgac aaacgtaata aaaaagctgt gacgcacata 41040 agtacgtgtctgtgtcattc atccatacct atatatggtg atagcccctt cctcaataca 41100 caccgagccgcgatggaccc cagaccactt gttctgctcc tcctcctagc gtcccatata 41160 agtacattccggcaaatgta ctttgaaggg gaaaccatcc atttccctat gggcatatat 41220 ggaaatgagaccaccctcta tatgaatgac atcatcctgg aaggaacacg cgccaatacg 41280 accacccgtacaatcagcct cacgaccacc aagaagaatg cgggaactaa cctgtacact 41340 gtgatctccgaaacgggaca caacgccacc tatctgataa ctgtacaacc gctgggacaa 41400 tcgatacaccacgcctacac ttgggctgga aatactttta ccttacaagg acaggtattt 41460 gaacacggtaattatacacg atgggtgcgg ctggagaatg cggaaccgaa actcattatc 41520 agctgggcattgtccaacag aacaataaac aaaggaccgg cctatactgc aaacatggac 41580 tttgatcccggaaacaacac cctcactctc caccctgtgc tgataacaga tgccgggatt 41640 ttccaatgcgtcattgatca gcaaacaaac ctaaccctca ccataaactt tacagtctcc 41700 gagaatccaccaatcgtagc acacctggat atccataaaa ctatttctag aacaattgcc 41760 atttgtagctgtttgcttat cgcggtaatt gcggtcttgt gttgcctacg tcagctcaat 41820 gtaaacgggcggggaaattc cgaaatgata taaaacaata aagcagtgtg cgtcatggaa 41880 acttttctcaggtgcttcct cattcacaca ggtatatata gggaatggaa aattagacag 41940 atacccacaccggaacaatg ctacttctca cagtagttct gttggtgggg gtcaccctcg 42000 ctgcggaccatcctactcta tacgctccga aagggggcag tatagaattg ggtgtggggg 42060 ctaaacagaaagggcaatac aaatttgaat ggcggtttgg aaatctaaaa attgtgatag 42120 ccgaaatgtcatccactaac caattagaaa tcaaatttcc cgataacggt ttccaaaatc 42180 gatccgagtttaaccccacc aaacataact taaccattca taatgccagc tacgaggaca 42240 gcggaacctactcactccac caggaagaaa atgatggcac ggaacacacg gacaacttca 42300 aagtgattgttcaaggtatg tcattatata catatttaca atatgcatta atatcaccta 42360 tctaatagagcattaattat ccagacccga ttccacgccc tgaagtcaag ggaaccacta 42420 tgcaaatcaacgggaaaact ttcaccaata tatcctgcca tctaccggcc ggttcctacg 42480 gcaatgtctcctggcattgg aattataccg acccaatcat agtcgggtac gaaaatcaga 42540 gcatgctcgttggaccttta ggggtaatgt attcatgtac ggcatccaat caagtctcaa 42600 aaaactccagtgcaataagt atggacaccg ccgaaccatc agagagtaag tagcgccctc 42660 tatagacattatatagaata taactgaaca cattaagaaa cctctgtaat tatttatagg 42720 agcggagtgcgcatatacag gatacattgc gggcattata atcttaggag tgctttgcat 42780 attgttcatttacctatatg caaatacccc tgaagtgcgg cagagaataa ccgaccaatt 42840 agaaaagcttctcggaacat tctgtgacgt cagtatagaa gacggaatac cggaacgcac 42900 cagaagaaacaaaaaaagaa tcatcttaaa ggagccctcc cataggtgga tctggattca 42960 gtcatttgcataatatgctg tgtcataacc gccaccatca ccatagcaat cattgggcgt 43020 aagtattgtgacgtaagaaa aggcatgtct aaaaaaacgg tcactcacca taatgctgcc 43080 cccgataggttgcgaccgcc ttccggagtt tgacgtagta tgcccgcgag actggatcgg 43140 atttcaaagcaagtgctact acttttcgga gtcagagtcc aattggagtg aagccgaaaa 43200 attttgtagacagcaagagg cggagctagc agttcggcgt tccgaggagg aaaaggtaaa 43260 aagttaaattccaggaaact cctaattccc cgaaaaatta caaaaattaa cggagaccct 43320 ttacaggagttccttctgcg ccaatgcgga acaggaacta actggctggg cgtaaccagg 43380 aagtcgaaggacggagctga ttgggtggat gcatcgtacg atgattacgt accatggtga 43440 gtcatgttatacgtcacatc cgggatgtga cgtatgcgga agttgatccg ggagtgaaaa 43500 cccggaagtaacctgttaat ttgcatacag gtatgaaatt cggggaggcg gagactgcgt 43560 gtatttaaatggagaccgag tgacgtcagc ctactgtgat acccagaagc tatttgtctg 43620 ttcctgtcaagattcgtatt cgtattggtt agaaaacaaa taaatcaata aactaattta 43680 tgatatcattcatatttatg ggtgtggttt tattatgcgt cataaaacta ttttgcgtat 43740 agcgacacgctgcggttatg gccggttatg actgcgttag tttttgaggt tattatacat 43800 catc 438042 178 PRT CELO Virus Position 794..1330 /note=ORF1 2 Met Asp Pro Phe GlySer Ser Ser Val Pro Pro Cys Ser Thr Ser Asp 1 5 10 15 Leu Pro Glu ProLys Leu Tyr Phe Val Arg Leu Ser Pro His Ala Val 20 25 30 Pro Pro Val ArgAla Thr His Gly Ala Ala Gly Tyr Asp Leu Phe Ser 35 40 45 Ala Tyr Asp IleLys Val Pro Ala Arg Gly Arg Ala Leu Val Pro Thr 50 55 60 Asp Leu Val PheGln Phe Pro Pro Gly Cys Tyr Gly Arg Ile Ala Pro 65 70 75 80 Arg Ser GlyLeu Ala Ala Lys Phe Phe Ile Asp Val Gly Ala Gly Val 85 90 95 Ile Asp ProAsp Tyr Arg Gly Asn Val Ser Val Val Leu Phe Asn Phe 100 105 110 Ser GluSer Ser Phe Asn Ile Arg Arg Gly Asp Arg Val Ala Gln Leu 115 120 125 IleLeu Glu Arg Ile Met Val Pro Glu Leu Ser Glu Leu Thr Gln Leu 130 135 140Gly Glu Thr Asp Arg Gly Ala Ser Gly Phe Gly Ser Thr Gly Met Gly 145 150155 160 Ala Val Asp Arg Asn Gln Arg Ser Val Leu Glu Trp Leu Thr Pro Gly165 170 175 Ser Arg 3 276 PRT CELO Virus Position 1999..2829 /note=ORF23 Met Ser Arg Glu Ser Glu Arg Tyr Trp Thr Leu Val His Ala Leu Ile 1 5 1015 Asp Arg Gly Val Val Ser Arg Glu Gln Trp Gln Met Val Asp Pro Ala 20 2530 Gln Tyr Gln Phe Tyr His Arg Ser Lys Gln Arg Gly Phe Lys Val Arg 35 4045 His Ile Leu Arg Asp Val Ile Arg His Met Cys Trp Ser Arg Thr Leu 50 5560 Leu Asp Tyr Met Ser Ser Ala Ser Thr Pro Ser Pro Asp Asp Val Leu 65 7075 80 Arg Asn Pro Leu Tyr Gln Leu Leu Leu Cys Asn Gly Tyr Asn Pro Ala 8590 95 Val Val Gly Thr Ala Leu Ile Arg Trp Ala Gly His Gln Ser Asn Arg100 105 110 Asn Thr Val Trp Ile Arg Gly Thr Pro Met Ser Gly Ala Pro TyrLeu 115 120 125 Ala Gln Ala Ile Ala Tyr Cys Ser Pro Leu Val Gly Ser ValAsp Trp 130 135 140 Arg Asn Lys Ser Asn Pro Phe Glu Gly Cys Pro Asp SerLeu Val Phe 145 150 155 160 Trp Trp Asp Gly Gly Tyr Val Tyr Asp Cys CysVal Gly Leu Val Lys 165 170 175 Gln Val Phe Arg Gly Glu His Val Ile LeuPro Pro Glu Gly Leu Arg 180 185 190 Gly Pro Asn Pro Cys Ser Glu Leu PheArg Thr Pro Val Leu Met Tyr 195 200 205 Ser Gln Ala Asp Ile Cys Met ThrArg Leu Arg Ser Gly Glu Leu Ser 210 215 220 Ala Glu His Ala Val Gly LeuArg Asp Cys Met Tyr Leu Ile Arg Leu 225 230 235 240 Thr Glu Asp Phe AspCys Ala Gly Gly Ile Ser Cys Ala Asp Val Lys 245 250 255 Gln Phe Val AlaTrp Ser Arg Glu His Pro Gly Glu Val Arg Glu Thr 260 265 270 His Glu LeuLys 275 4 104 PRT CELO Virus Position 3781..4095 /note=ORF3 4 Met GlyVal Glu Gly Met Trp Asn Val Phe Leu Phe Ser Leu Gln Val 1 5 10 15 AlaAla Leu Pro Ser Ile Lys Cys Ser Ile Asn Gly Ser Gly Phe Ser 20 25 30 SerThr Lys Gly Arg Gln Tyr Arg Glu Ala Trp Gly Ala Ile Ser Pro 35 40 45 SerAsp Ser Met Glu Leu Ile Arg Leu Ser Glu Ile Ala Ser Gly Lys 50 55 60 HisAla His Lys Ala Leu Lys Arg Leu Leu Ala Leu Glu Ser Leu Pro 65 70 75 80Pro Gln Ser Thr Arg Val Phe Ser Ser Pro Arg Ser His Arg Arg Met 85 90 95Ala Leu Ala Ala Thr Phe Pro Ser 100 5 136 PRT CELO Virus Position5963..6373 /note=ORF4 5 Met Val Asp Val Glu Met Phe Gly Cys Gly Gly LeuLeu Val Ser His 1 5 10 15 Leu His Lys Phe Gly Thr Glu Arg Ala Cys LeuArg Gly Asp Gly Ala 20 25 30 Val Phe Pro Ala Val Glu Ile Gly Leu Asp GlnLeu Gln Val Pro Gly 35 40 45 Arg Leu Phe Asp Gly Trp Asn His Val Leu PheArg Ser Asp Glu Asp 50 55 60 Asp Arg Phe Gly Asp Arg Val Gln His Val AlaArg Asp Glu Arg Pro 65 70 75 80 Gln Gln Met Arg Leu Ala Gly Ser Gly GlySer Val Asp Asp Pro Asp 85 90 95 Asp Gly Leu Leu Ala His Val Asp Gly ArgGln Leu Ser Val Leu Glu 100 105 110 Val Ala Thr Val His Leu Phe Leu GlyPhe Asn Phe Phe Val Gly Phe 115 120 125 Glu Lys Leu Leu Ile Asn Ala Pro130 135 6 378 PRT CELO Virus Position 12193..13329 /gene L1 /Product L152K 6 Met His Pro Val Leu Gln Ser Val Arg Asn Ala Ser Val Ser Ala Gly 15 10 15 Gly Pro His Gln Gln Gln Pro Gln Gln Gln Gln His Gly Val Ser Ser20 25 30 Val Arg Arg Pro Pro Ser Pro Pro Arg Tyr Pro Ala Gln His Ala Tyr35 40 45 Pro Gly Ala Gly Ala Thr Pro Thr Ala Gly Arg Gly Asp Phe Asp Gly50 55 60 Ala Leu Asp Pro Asp Glu Gly Pro Val Ala Cys Gly Leu Ala Ala Gly65 70 75 80 Ala Gly Val Asp Glu Val Arg Met Arg Glu Arg Asp Ala Ala ArgArg 85 90 95 Ala Thr Val Pro Glu Ile Asn Leu Phe Lys Ala Arg Arg Asp ValVal 100 105 110 Pro Asn Gly Asp Tyr Glu Arg Asp Leu Met Tyr His Ser GlyGln Ala 115 120 125 Ile Asp Ile Asp Arg Gln Arg Val Leu Thr Pro Glu AspPhe Lys Gly 130 135 140 Ser Glu Pro Ala Phe Thr Pro Ala Val Asn His MetArg Ala Ala Glu 145 150 155 160 Leu Lys Arg Ala Ala Glu Gln Thr Ala PheGly Glu Glu Leu Arg Asn 165 170 175 Thr Cys His Gln Thr Arg Ile Arg ThrAla Leu Leu Arg Pro Glu Ile 180 185 190 Gly Ala Gly Ile Tyr Tyr Leu TyrAsp Phe Val Gln Thr Tyr Leu Glu 195 200 205 His Pro Asp Gly Arg Val LysLeu Asn Pro Gln Leu Val Leu Val Ala 210 215 220 Gln His Ala Gly Asn ThrMet Leu Ala Gln Arg Leu Trp Ala Ile Ala 225 230 235 240 Glu Glu Lys AsnAla Trp Leu Arg Asp Leu Ile Glu Met Ala Tyr Met 245 250 255 Ile Val AsnAsp Pro Tyr Leu Asn Thr Glu Gln Gln Leu Ser Ala Ile 260 265 270 Cys ThrThr Val Val Glu Leu Ser Met Lys Tyr Ala Lys Leu Ala Ala 275 280 285 LysAsn Gly Tyr Pro Ser Met Ala Gln Met Ala Lys Ala Gln Glu Phe 290 295 300Phe Tyr Arg Val Met Gln Ala Val Leu Asp Leu Gly Val Gln Val Gly 305 310315 320 Val Tyr Asn Asn Arg Pro Ala Arg Tyr Arg Gln Lys Arg Met Ser Glu325 330 335 Ile Pro Gln Met Thr Asp Ala Glu Tyr Met Phe Gly Leu Thr GlnAla 340 345 350 Leu Glu Ser Arg Pro Pro Gln Gly Glu Ser Phe Ala Asp GluGly Pro 355 360 365 Ser Glu Ser Asp Asp Glu Asp Asp Phe Ile 370 375 7575 PRT CELO Virus Position 13316..15043 /gene L1 /product L1 IIIa 7 MetThr Ser Ser Asp Thr Phe Leu Ala Leu Ala Pro Tyr Gly Arg Gln 1 5 10 15Glu Val Ala Asp Ala Leu Ser Ser Leu Pro Asp Gly Lys Asp Ala Arg 20 25 30Ser Leu Arg His Ala Pro Tyr Ala Asn Arg Leu Ile Lys Leu Gln Ser 35 40 45Ala Met Val Pro Pro Lys Val Asp Gly Thr Ser Glu Arg Val Ala Glu 50 55 60Ile Val Lys Gly Leu Ala Glu Gln Gly Ala Ile Tyr Pro Asp Gln Met 65 70 7580 Gly Ala Ile His Ser Asp Leu Leu Asn Arg Ala Tyr Thr Trp Asn Ser 85 9095 Met Gly Val Gln Glu Ser Ile Gln Ala Leu Val Asn Asp Val Ile His 100105 110 Gly Gln Asn Arg Thr Leu Gln Asp Glu Leu Ala Arg Thr Lys Glu Ile115 120 125 Ala Asn Ala Ser Leu Leu Thr Gln Phe Phe Asp Ser Leu Tyr LysThr 130 135 140 Val Asp Arg Gly Gln Arg Asn Phe Glu Gly Phe Lys Lys LeuLeu Arg 145 150 155 160 Leu Phe Val Asn Asn Val Pro Asn Ala Glu Val TyrGly Ser Ser Gly 165 170 175 Ser Phe Ser Val Gln Ile Asn Leu Gly Gly SerSer Gln Asn Ile Asn 180 185 190 Leu Thr Asn Ala Phe Glu Asn Leu Lys ProIle Trp Gly Ala Arg Trp 195 200 205 Asp Ala Val Asn Asn Pro Arg Ile GlyAla Leu Leu Thr Pro Asn Thr 210 215 220 Arg Ala Leu Leu Phe Phe Val SerSer Phe Tyr Asp Tyr Gly Ala Met 225 230 235 240 Glu Pro Gly Ser Tyr LeuAsp Asn Ile Met Arg Leu Tyr Lys Glu Ala 245 250 255 Ile Arg Ala Asp ValAsp Ala Glu Gly Asp Ala Ile Met Glu Leu Gly 260 265 270 Glu Ala Gly AlaAsn Leu Asn Leu Arg Phe Asn Asp Tyr Lys Asp Thr 275 280 285 Leu Asn TyrLeu Leu Gln Asn Arg Glu Val Val Pro Asp Thr Ala Pro 290 295 300 Leu GluLeu Ser Ala Glu Gln Glu Met Leu Leu Lys Tyr Leu Met Arg 305 310 315 320Gln Leu Arg Gln Ala Leu Lys Asp Gly Val Pro Ala Asp Ile Ser Ile 325 330335 Ser Thr Met Thr Gln Tyr Leu Asp Pro Arg Leu Tyr Gln Thr Asn Lys 340345 350 Val Phe Val Glu Lys Leu Gln Asn Tyr Leu Leu Ala Ala Gln Ala Arg355 360 365 Asn Pro Val Tyr Tyr Arg Leu Leu Val Leu Asp Pro Asn Trp ArgPro 370 375 380 Pro Ala Gly Leu Tyr Thr Gly Asn Tyr Val Ile Pro Asp ArgTyr Asp 385 390 395 400 Phe Glu Asp Val Gln Ser Glu Leu Glu Tyr Ala GlyPro Ser Arg Asp 405 410 415 Glu Tyr Phe Asp Asp Ser Leu Phe Ala Pro GlyPro Gln Arg Arg Leu 420 425 430 Asn Ser Ala Glu Glu Ala Gln Leu Glu ArgAsp Ile Glu Ser Leu Thr 435 440 445 Gly His Ile Asp Glu Glu Leu Gly ValGln Ser Gln Ala Gly Trp Leu 450 455 460 Ala Asp His Arg Leu Pro Val AlaPhe Asp Gly Ala Leu Ser Leu Thr 465 470 475 480 Glu Arg Asn Ala Tyr AsnThr Pro Leu Pro Pro Asp Ser His Met Arg 485 490 495 Ser Arg Ser Ser SerVal Ala Ser Asp Leu Gly Leu Leu Asn Leu Ser 500 505 510 Gly Thr Gly GlyPro Gly Phe Phe Ala Ser Leu Arg Pro Ser Ile Gly 515 520 525 Ser Arg GlnPro Thr Gly Thr Ala Val Gly Leu Arg Pro Thr Thr Pro 530 535 540 Tyr SerGly Ser Gly Cys Met Arg Gly Thr Gly Leu Ala Arg Lys Val 545 550 555 560Leu Asn Pro Ala Ala Ser Arg Arg Gly Arg Lys Leu Arg Phe Tyr 565 570 5758 515 PRT CELO Virus Position 15110..16657 /gene L2 /product penton base8 Met Tyr Arg Ser Leu Arg Pro Pro Thr Ser Ile Pro Pro Pro Pro Pro 1 5 1015 Ser Gly Pro Ser Pro Tyr Pro Ala Met Ile Asn Gly Tyr Pro Pro Asp 20 2530 Val Pro Val Gly Ser Pro Ala Asn Gly Asp Ala Glu Leu Phe Val Pro 35 4045 Leu Gln Arg Val Met Pro Pro Thr Gly Gly Arg Asn Ser Ile Arg Tyr 50 5560 Arg Asn Tyr Ala Pro Cys Gln Asn Thr Thr Lys Phe Phe Tyr Val Asp 65 7075 80 Asn Lys Leu Ser Asp Leu Asp Thr Tyr Asn Glu Asp Ala Asn His Ser 8590 95 Asn Phe Arg Thr Thr Val Ile His Asn Gln Asp Leu Asp Pro Ser Thr100 105 110 Ala Ala Thr Glu Thr Ile Gln Leu Asp Asn Arg Ser Cys Trp GlyGly 115 120 125 Glu Leu Lys Thr Ala Val Lys Thr Asn Cys Pro Asn Ile SerSer Phe 130 135 140 Phe Gln Ser Asp Thr Val Arg Val Arg Leu Met Ser LysArg Asp Pro 145 150 155 160 Gly Gly Thr Asp Pro Asp Ala Gly Val Asn AsnPro Pro Gly Ala Glu 165 170 175 Tyr Lys Trp Tyr Asp Leu Arg Ile Pro GluGly Asn Tyr Ala Leu Asn 180 185 190 Glu Ile Ile Asp Leu Leu Asn Glu GlyIle Val Gln Leu Tyr Leu Gln 195 200 205 Glu Gly Arg Gln Asn Asn Val LeuLys Ser Asp Ile Gly Val Lys Phe 210 215 220 Asp Thr Arg Tyr Leu Asp LeuLeu Lys Asp Pro Val Thr Gly Leu Val 225 230 235 240 Thr Pro Gly Thr TyrVal Tyr Lys Gly Tyr His Pro Asp Ile Ile Leu 245 250 255 Leu Pro Gly CysAla Val Asp Phe Thr Phe Ser Arg Leu Ser Leu Leu 260 265 270 Leu Gly IleAla Lys Arg Glu Pro Tyr Ser Lys Gly Phe Thr Ile Thr 275 280 285 Tyr GluAsp Leu Gln Gly Gly Asn Val Pro Ala Leu Leu Asp Leu Ser 290 295 300 SerVal Gln Val Asp Asp Gln Asp Glu Asp Val Ile Val Val Ala Asp 305 310 315320 Ala Arg Pro Leu Leu Lys Asp Ser Lys Gly Val Ser Tyr Asn Val Ile 325330 335 Thr Thr Gly Val Thr Gln Pro Gln Thr Ala Tyr Arg Ser Trp Leu Leu340 345 350 Ala Tyr His Thr Leu Asp Ser Pro Ala Arg Asn Lys Thr Leu LeuThr 355 360 365 Val Pro Asp Met Ala Gly Gly Ile Gly Ala Met Tyr Thr SerMet Pro 370 375 380 Asp Thr Phe Thr Ala Pro Ala Gly Phe Lys Glu Asp AsnThr Thr Asn 385 390 395 400 Leu Cys Pro Val Val Ala Met Asn Leu Phe ProSer Phe Asn Lys Val 405 410 415 Phe Tyr Gln Gly Ala Ser Ala Tyr Val GlnArg Leu Glu Asn Ala Thr 420 425 430 Gln Ser Ala Thr Ala Ala Phe Asn ArgPhe Pro Glu Asn Glu Ile Leu 435 440 445 Lys Gln Ala Pro Pro Met Asn ValSer Ser Val Cys Asp Asn Gln Pro 450 455 460 Ala Val Val Gln Gln Gly ValLeu Pro Leu Lys Asn Ser Leu Ser Gly 465 470 475 480 Leu Gln Arg Val LeuIle Thr Asp Asp Arg Arg Arg Pro Ile Pro Tyr 485 490 495 Val Tyr Lys ThrIle Ala Thr Val Gln Pro Arg Val Leu Ser Ser Ser 500 505 510 Thr Leu Gln515 9 72 PRT CELO Virus Position 16679..16897 /gene L2 /product L2pVII 9Met Ser Ile Leu Ile Ser Pro Ser Asp Asn Arg Gly Trp Gly Ala Asn 1 5 1015 Met Arg Tyr Arg Arg Arg Ala Ser Met Arg Gly Val Gly Arg Arg Arg 20 2530 Leu Thr Leu Arg Gln Leu Leu Gly Leu Gly Ser Arg Arg Arg Arg Arg 35 4045 Ser Arg Pro Thr Thr Val Ser Asn Arg Leu Val Val Val Ser Thr Arg 50 5560 Arg Arg Ser Ser Arg Arg Arg Arg 65 70 10 188 PRT CELO Virus Position16929..17495 /gene L2 /product L2 mu (pX, 11K) 10 Met Cys Ala Val AlaIle His Arg Ser Asp Val Val Met Pro Ser Val 1 5 10 15 Leu Leu Thr GlyGly Arg Thr Ala Lys Gly Lys Lys Arg Ala Ser Arg 20 25 30 Arg Arg Val LysVal Pro Lys Leu Pro Lys Gly Ala Arg Arg Lys Arg 35 40 45 Ala Ser Val ThrPro Val Pro Thr Val Ala Thr Ala Thr Ala Ser Glu 50 55 60 Arg Ala Ala LeuThr Asn Leu Ala Arg Arg Leu Gln Arg Gly Asp Tyr 65 70 75 80 Ala Ala TrpArg Pro Ala Asp Tyr Thr Ser Pro Ala Val Ser Glu Ala 85 90 95 Ala Arg AlaAla Ala Ser Ser Gly Thr Pro Ala Thr Ala Arg Asp Leu 100 105 110 Ala ThrGly Thr Leu Ala Arg Ala Val Pro Met Thr Gly Thr Gly Gly 115 120 125 ArgArg Arg Lys Arg Thr Ala Thr Arg Arg Arg Ser Leu Lys Gly Gly 130 135 140Phe Leu Pro Ala Leu Ile Pro Ile Ile Ala Ala Ala Ile Gly Ala Ile 145 150155 160 Pro Gly Ile Ala Gly Thr Ala Val Gly Ile Ala Asn Leu Lys Glu Gln165 170 175 Gln Arg Gln Phe Asn Lys Ile Tyr Gly Asp Lys Lys 180 185 11223 PRT CELO Virus Position 17559..18230 /gene L3 /product L3 pVI 11 MetAsp Tyr Ala Ala Leu Ser Pro His Leu Gly Gly Trp Ala Leu Arg 1 5 10 15Asp His His Ile Gly Asp Ser Ser Leu Arg Gly Gly Ala Ile Asn Trp 20 25 30Gly Asn Leu Gly Ser Arg Ile Thr Ser Ala Leu Asn Ser Thr Gly Arg 35 40 45Trp Leu Tyr Asn Thr Gly Asn Arg Phe Val His Ser Asn Thr Phe Asn 50 55 60Gln Ile Lys Gln Gly Ile Gln Asp Ser Gly Val Ile Arg Asn Val Ala 65 70 7580 Asn Leu Ala Gly Glu Thr Leu Gly Ala Leu Thr Asp Ile Gly Arg Leu 85 9095 Lys Leu Gln Gln Asp Leu Glu Lys Leu Arg Arg Lys Ala Leu Gly Glu 100105 110 Glu Gly Pro Ala Thr Gln Ala Glu Leu Gln Ala Leu Ile Gln Ala Leu115 120 125 Gln Ala Gln Val Ala Ala Gly Glu Pro Pro Ala Ala Pro Ala AlaPro 130 135 140 Ala Pro Ala Pro Pro Leu Val Pro Thr Thr Arg Pro Ile ProGlu Met 145 150 155 160 Val Thr Glu Val Lys Pro Pro Val Thr Ser Ser AlaPro Ala Val Pro 165 170 175 Val Asp Val Pro Thr Thr Leu Glu Met Arg ProPro Pro Pro Lys Arg 180 185 190 Arg Arg Lys Arg Ala Arg Pro Gly Gln TrpArg Ala Arg Leu Asp Ser 195 200 205 Leu Ser Gly Thr Gly Val Ala Thr AlaThr Arg Arg Met Cys Tyr 210 215 220 12 942 PRT CELO Virus Position18289..21117 /gene L3 /product L3 hexon 12 Met Thr Ala Leu Thr Pro AspLeu Thr Thr Ala Thr Pro Arg Leu Gln 1 5 10 15 Tyr Phe His Ile Ala GlyPro Gly Thr Arg Glu Tyr Leu Ser Glu Asp 20 25 30 Leu Gln Gln Phe Ile SerAla Thr Gly Ser Tyr Phe Asp Leu Lys Asn 35 40 45 Lys Phe Arg Gln Thr ValVal Ala Pro Thr Arg Asn Val Thr Thr Glu 50 55 60 Lys Ala Gln Arg Leu GlnIle Arg Phe Tyr Pro Ile Gln Thr Asp Asp 65 70 75 80 Thr Pro Asn Ser TyrArg Val Arg Tyr Ser Val Asn Val Gly Asp Ser 85 90 95 Trp Val Leu Asp MetGly Ala Thr Tyr Phe Asp Ile Lys Gly Val Leu 100 105 110 Asp Arg Gly ProSer Phe Lys Pro Tyr Gly Gly Thr Ala Tyr Asn Pro 115 120 125 Leu Ala ProArg Glu Ala Ile Phe Asn Thr Trp Val Glu Ser Thr Gly 130 135 140 Pro GlnThr Asn Val Val Gly Gln Met Thr Asn Val Tyr Thr Asn Gln 145 150 155 160Thr Arg Asn Asp Lys Thr Ala Thr Leu Gln Gln Val Asn Ser Ile Ser 165 170175 Gly Val Val Pro Asn Val Asn Leu Gly Pro Gly Leu Ser Gln Leu Ala 180185 190 Ser Arg Ala Asp Val Asp Asn Ile Gly Val Val Gly Arg Phe Ala Lys195 200 205 Val Asp Ser Ala Gly Val Lys Gln Ala Tyr Gly Ala Tyr Val LysPro 210 215 220 Val Lys Asp Asp Gly Ser Gln Ser Leu Asn Gln Thr Ala TyrTrp Leu 225 230 235 240 Met Asp Asn Gly Gly Thr Asn Tyr Leu Gly Ala LeuAla Val Glu Asp 245 250 255 Tyr Thr Gln Thr Leu Ser Tyr Pro Asp Thr ValLeu Val Thr Pro Pro 260 265 270 Thr Ala Tyr Gln Gln Val Asn Ser Gly ThrMet Arg Ala Cys Arg Pro 275 280 285 Asn Tyr Ile Gly Phe Arg Asp Asn PheIle Asn Leu Leu Tyr His Asp 290 295 300 Ser Gly Val Cys Ser Gly Thr LeuAsn Ser Glu Arg Ser Gly Met Asn 305 310 315 320 Val Val Val Glu Leu GlnAsp Arg Asn Thr Glu Leu Ser Tyr Gln Tyr 325 330 335 Met Leu Ala Asp MetMet Ser Arg His His Tyr Phe Ala Leu Trp Asn 340 345 350 Gln Ala Val AspGln Tyr Asp His Asp Val Arg Val Phe Asn Asn Asp 355 360 365 Gly Tyr GluGlu Gly Val Pro Thr Tyr Ala Phe Leu Pro Asp Gly His 370 375 380 Gly AlaGly Glu Asp Asn Gly Pro Asp Leu Ser Asn Val Lys Ile Tyr 385 390 395 400Thr Asn Gly Gln Gln Asp Lys Gly Asn Val Val Ala Gly Thr Val Ser 405 410415 Thr Gln Leu Asn Phe Gly Thr Ile Pro Ser Tyr Glu Ile Asp Ile Ala 420425 430 Ala Ala Thr Arg Arg Asn Phe Ile Met Ser Asn Ile Ala Asp Tyr Leu435 440 445 Pro Asp Lys Tyr Lys Phe Ser Ile Arg Gly Phe Asp Pro Val ThrAsp 450 455 460 Asn Ile Asp Pro Thr Thr Tyr Phe Tyr Met Asn Arg Arg ValPro Leu 465 470 475 480 Thr Asn Val Val Asp Leu Phe Thr Asn Ile Gly AlaArg Trp Ser Val 485 490 495 Asp Gln Met Asp Asn Val Asn Pro Phe Asn HisHis Arg Asn Trp Gly 500 505 510 Leu Lys Tyr Arg Ser Gln Leu Leu Gly AsnSer Arg Tyr Cys Arg Phe 515 520 525 His Ile Gln Val Pro Gln Lys Tyr PheAla Ile Lys Asn Leu Leu Leu 530 535 540 Leu Pro Gly Thr Tyr Thr Tyr GluTrp Val Leu Arg Lys Asp Pro Asn 545 550 555 560 Met Ile Leu Gln Ser SerLeu Gly Asn Asp Leu Arg Ala Asp Gly Ala 565 570 575 Gln Ile Val Tyr ThrGlu Val Asn Leu Met Ala Asn Phe Met Pro Met 580 585 590 Asp His Asn ThrSer Asn Gln Leu Glu Leu Met Leu Arg Asn Ala Thr 595 600 605 Asn Asp GlnThr Phe Ala Asp Tyr Leu Gly Ala Lys Asn Ala Leu Tyr 610 615 620 Asn ValPro Ala Gly Ser Thr Leu Leu Thr Ile Asn Ile Pro Ala Arg 625 630 635 640Thr Trp Glu Gly Met Arg Gly Trp Ser Phe Thr Arg Leu Lys Ala Ser 645 650655 Glu Thr Pro Gln Leu Gly Ala Gln Tyr Asp Val Gly Phe Lys Tyr Ser 660665 670 Gly Ser Ile Pro Tyr Ser Asp Gly Thr Phe Tyr Leu Ser His Thr Phe675 680 685 Arg Ser Met Ser Val Leu Phe Asp Thr Ser Ile Asn Trp Pro GlyAsn 690 695 700 Asp Arg Leu Leu Thr Pro Asn Leu Phe Glu Ile Lys Arg ProVal Ala 705 710 715 720 Thr Asp Ser Glu Gly Phe Thr Met Ser Gln Cys AspMet Thr Lys Asp 725 730 735 Trp Phe Leu Val Gln Met Ala Thr Asn Tyr AsnTyr Val Tyr Asn Gly 740 745 750 Tyr Arg Phe Trp Pro Asp Arg His Tyr PheHis Tyr Asp Phe Leu Arg 755 760 765 Asn Phe Asp Pro Met Ser Arg Gln GlyPro Asn Phe Leu Asp Thr Thr 770 775 780 Leu Tyr Asp Leu Val Ser Ser ThrPro Val Val Asn Asp Thr Gly Ser 785 790 795 800 Gln Pro Ser Gln Asp AsnVal Arg Asn Asn Ser Gly Phe Ile Ala Pro 805 810 815 Arg Ser Trp Pro ValTrp Thr Ala Gln Gln Gly Glu Ala Trp Pro Ala 820 825 830 Asn Trp Pro TyrPro Leu Ile Gly Asn Asp Ala Ile Ser Ser Asn Gln 835 840 845 Thr Val AsnTyr Lys Lys Phe Leu Cys Asp Asn Tyr Leu Trp Thr Val 850 855 860 Pro PheSer Ser Asp Phe Met Tyr Met Gly Glu Leu Thr Asp Leu Gly 865 870 875 880Gln Asn Pro Met Tyr Thr Asn Asn Ser His Ser Met Val Ile Asn Phe 885 890895 Glu Leu Asp Pro Met Asp Glu Asn Thr Tyr Val Tyr Met Leu Tyr Gly 900905 910 Val Phe Asp Thr Val Arg Val Asn Gln Pro Glu Arg Asn Val Leu Ala915 920 925 Met Ala Tyr Phe Arg Thr Pro Phe Ala Thr Gly Asn Ala Val 930935 940 13 206 PRT CELO Virus Position 21134..21754 /gene L3 /product L3protease 13 Met Ser Gly Thr Thr Glu Thr Gln Leu Arg Asp Leu Leu Ser SerMet 1 5 10 15 His Leu Arg His Arg Phe Leu Gly Val Phe Asp Lys Ser PhePro Gly 20 25 30 Phe Leu Asp Pro His Val Pro Ala Ser Ala Ile Val Asn ThrGly Ser 35 40 45 Arg Ala Ser Gly Gly Met His Trp Ile Gly Phe Ala Phe AspPro Ala 50 55 60 Ala Gly Arg Cys Tyr Met Phe Asp Pro Phe Gly Trp Ser AspGln Lys 65 70 75 80 Leu Trp Glu Leu Tyr Arg Val Lys Tyr Asn Ala Phe MetArg Arg Thr 85 90 95 Gly Leu Arg Gln Pro Asp Arg Cys Phe Thr Leu Val ArgSer Thr Glu 100 105 110 Ala Val Gln Cys Pro Cys Ser Ala Ala Cys Gly LeuPhe Ser Ala Leu 115 120 125 Phe Ile Val Ser Phe Asp Arg Tyr Arg Ser LysPro Met Asp Gly Asn 130 135 140 Pro Val Ile Asp Thr Val Val Gly Val LysHis Glu Asn Met Asn Ser 145 150 155 160 Pro Pro Tyr Arg Asp Ile Leu HisArg Asn Gln Glu Arg Thr Tyr Tyr 165 170 175 Trp Trp Thr Lys Asn Ser AlaTyr Phe Arg Ala His Gln Glu Glu Leu 180 185 190 Arg Arg Glu Thr Ala LeuAsn Ala Leu Pro Glu Asn His Val 195 200 205 14 984 PRT CELO VirusPosition 23680..26634 /gene L4 /product L4 100K 14 Met Ala Asp Lys IleThr Arg Glu Glu Lys Thr Ile Ala Thr Leu Asp 1 5 10 15 Leu Val Leu ArgVal Val Val Asp Ala Gly Asn Trp Asp Val Phe Ser 20 25 30 Lys Arg Leu ValArg Tyr Thr Arg Glu Gln Tyr Gly Ile Glu Leu Pro 35 40 45 Glu Asp Ile GlyAsp Leu Pro Asp Thr Ser Glu Val Ser Lys Val Leu 50 55 60 Leu Ser His LeuGly Glu Asp Lys Ala Val Leu Ser Ala Tyr Arg Ile 65 70 75 80 Ala Glu LeuThr Gln Pro Ser Glu Met Asp Arg Ala Lys Val Thr Glu 85 90 95 Gly Gly LeuAla Val Leu Asn Ala Ser Arg Asp Glu Ser Glu Ala Gln 100 105 110 Asn ProSer Asn Pro Glu Pro Glu Ser Ile Glu Ser Asp Ala Val Glu 115 120 125 AspLeu Gly Val Ala Ala Glu Ser Asp Pro Ser Asp Asp Glu Pro Asp 130 135 140Pro Glu Pro Glu Tyr Asp His Arg Glu Ala Asp His Asp Ser Asp Ala 145 150155 160 Asp Ser Gly Tyr Tyr Ser Ala Asp Gly Gly Arg Pro Gly Thr Pro Val165 170 175 Asp Glu Glu Pro Gln Asp Asp Ser Pro Ser Ser Glu Glu Thr AlaSer 180 185 190 Thr Val Ile Glu Glu Ala Gln Thr Ser Ala Ser Asn Asp SerHis Asp 195 200 205 Asp Asp Thr His Arg Asp Asp Gly Ser Ala Ser Glu GluAsp Leu Glu 210 215 220 Arg Asp Ala Leu Val Ala Pro Ala Asp Pro Phe ProAsn Leu Arg Lys 225 230 235 240 Cys Phe Glu Arg Gln Ala Met Met Leu ThrGly Ala Leu Lys Asp Ala 245 250 255 Ala Asp Thr Ala Asp Pro Pro Glu ThrLeu Ser Val Asp Ser Val Gln 260 265 270 Arg Gln Leu Glu Arg Phe Val PheAsn Pro Asp Arg Arg Val Pro Ala 275 280 285 Glu His Leu Glu Val Arg TyrAsn Phe Tyr Pro Pro Phe Leu Thr Pro 290 295 300 Lys Ala Ile Ala Ser TyrHis Ile Phe Ala Val Thr Ala Ser Ile Pro 305 310 315 320 Leu Ser Cys LysAla Asn Arg Ser Gly Ser Asp Leu Leu Ala Lys Ala 325 330 335 Lys Glu SerThr Phe Phe Lys Arg Leu Pro Lys Trp Arg Leu Gly Ile 340 345 350 Glu IleAsp Asp Gly Leu Gly Thr Glu Val Thr Ala Val Thr Glu Leu 355 360 365 GluGlu Ala Lys Met Val Pro Leu Lys Asp Asp Val Ser Arg Leu Gln 370 375 380Trp Ala Lys Met Arg Gly Glu His Ile Arg Phe Phe Ser Tyr Pro Ser 385 390395 400 Leu His Met Pro Pro Lys Ile Ser Arg Met Leu Met Glu Thr Leu Leu405 410 415 Gln Pro Phe Ala Asp Glu Asn Gln Lys Ala Glu Glu Ala Leu ProCys 420 425 430 Leu Ser Asp Glu Glu Val Leu Ala Ile Val Asp Pro Thr GlyArg Leu 435 440 445 His Gly Glu Asp Ala Leu Lys Ala Val Glu Lys Arg ArgAla Ala Val 450 455 460 Thr Met Ala Val Arg Tyr Thr Ala Thr Leu Glu LeuMet Glu Arg Val 465 470 475 480 Phe Arg Glu Pro Ser Met Val Lys Lys MetGln Glu Val Leu His His 485 490 495 Thr Phe His His Gly Phe Val Ala LeuVal Arg Glu Thr Ala Lys Val 500 505 510 Asn Leu Ser Asn Tyr Ala Thr PheHis Gly Leu Thr Tyr Asn Asn Pro 515 520 525 Leu Asn Asn Cys Ile Met SerLys Leu Leu Glu Gly Ala Asp Lys Glu 530 535 540 Asp Tyr Val Val Asp SerIle Tyr Leu Phe Leu Val Leu Thr Trp Gln 545 550 555 560 Thr Ala Met GlyMet Trp Gln Gln Ala Ile Asp Asp Met Thr Ile Gln 565 570 575 Met Tyr ThrGlu Val Phe Thr Lys Asn Lys Tyr Arg Leu Tyr Ser Leu 580 585 590 Pro AsnPro Thr Ala Ile Gly Lys Ala Ile Val Asp Ile Leu Met Asp 595 600 605 TyrAsp Arg Leu Thr Glu Glu Met Arg Lys Ala Leu Pro Asn Phe Thr 610 615 620Cys Gln Ser Gln Ile Thr Ala Phe Arg His Phe Leu Leu Glu Arg Ser 625 630635 640 Asn Ile Pro Ala Val Ala Ala Pro Phe Met Pro Ser Asp Phe Val Pro645 650 655 Leu Ala Tyr Lys Gln Ser Pro Pro Leu Leu Trp Asp Gln Val TyrLeu 660 665 670 Leu Gln Leu Ala Phe Tyr Leu Thr Lys His Gly Gly Tyr LeuTrp Glu 675 680 685 Ala Pro Glu Glu Glu Ala Asn Asn Pro Ser Asn Arg ThrTyr Cys Pro 690 695 700 Cys Asn Leu Cys Ser Pro His Arg Met Pro Gly HisAsn Ala Ala Leu 705 710 715 720 His Asn Glu Ile Leu Ala Ile Gly Thr PheGlu Ile Arg Ser Pro Asp 725 730 735 Gly Lys Thr Phe Lys Leu Thr Pro GluLeu Trp Thr Asn Ala Tyr Leu 740 745 750 Asp Lys Phe Asp Ala Glu Asp PheHis Pro Phe Thr Val Phe His Tyr 755 760 765 Pro Glu Asn Ala Ser Arg PheAla Ser Thr Leu Lys Ala Cys Val Thr 770 775 780 Gln Ser Pro Glu Ile LeuSer Leu Ile Arg Gln Ile Gln Glu Ser Arg 785 790 795 800 Glu Glu Phe LeuLeu Thr Lys Gly Lys Gly Val Tyr Lys Asp Pro Asn 805 810 815 Thr Gly GluThr Ile Ser Arg Gln Pro Arg Asp Thr Ala Arg Ala Gln 820 825 830 His AlaGly Asp Gly Gln Ala Leu Pro Ala Pro Gly Ala Tyr Thr Thr 835 840 845 GlyGly Asn Arg Ala Glu Thr Ala Pro Ala Gly Ala Val Arg Leu Ala 850 855 860Pro Asp Tyr Gln Asp Gly Gln Phe Pro Ile Ala Lys Val Gly Pro His 865 870875 880 Tyr His Gly Pro Lys Asn Val Arg Arg Glu Asp Gln Gly Tyr Arg Gly885 890 895 Gly Pro Gly Gly Val Arg Gly Glu Arg Glu Val Val Leu Ser ArgArg 900 905 910 Ala Gly Gly Arg Arg Phe Gly Arg Arg Asn Thr Arg Gln SerGly Tyr 915 920 925 Asn Glu Arg Ala Asn Arg Tyr Phe Gly Arg Gly Gly GlyGly Ser Val 930 935 940 Arg Gly Gln Gln Gly Glu His Pro Thr Thr Ser ProSer Ala Ser Glu 945 950 955 960 Pro Pro Ala Pro Ser Arg Ile Leu Ala ArgGly Thr Pro Pro Ser Pro 965 970 975 Glu Arg Arg Asp Arg Gln Glu Glu 98015 245 PRT CELO Virus Position 27149..27886 /gene L4 /product L4 pVIII15 Met Asn Leu Met Asn Ala Thr Pro Thr Glu Tyr Val Trp Lys Tyr Asn 1 510 15 Pro Val Ser Gly Ile Pro Ala Gly Ala Gln Gln Asn Tyr Gly Ala Thr 2025 30 Ile Asp Trp Val Leu Pro Gly Gly Thr Gly Phe Ala Ile Ala Thr Asn 3540 45 Asp Ile Arg Arg Gln Thr Leu Asn Pro Ala Val Thr Arg Ala Ile Thr 5055 60 Ala Arg Phe Glu Ala Glu Ser Asp Gln Gln Pro Tyr Ala Ser Pro His 6570 75 80 Glu Thr Asn Val Ile Ala Ala Asn Val Leu Asp Ser Gly Tyr Pro Lys85 90 95 Ser Gly Leu Tyr Pro Leu Glu Leu Ser Gly Asn Gln Arg Val Gln Leu100 105 110 Ala Gly Gly Leu Met Val Gly Arg Thr Glu Gly Arg Met Gln LeuAla 115 120 125 Gly Gly Leu Thr Glu Gly Arg Val Gln Leu Ser Gly Gly PheHis Gly 130 135 140 Arg Pro Leu Val Arg Gly Arg Ser Arg Arg Pro Pro ArgTrp Cys Gly 145 150 155 160 Ala Glu Leu Thr Gly Asn Gly Leu Pro Glu GlnAla Glu Val Thr Ser 165 170 175 Asp Thr Tyr Lys Tyr Phe Leu Arg Thr GlnGly Pro Ser Gln Val Val 180 185 190 Glu Glu Pro Gly Val Phe Ser Gln ArgGln Phe Met Thr Thr Phe Leu 195 200 205 Pro Ser Val Val Pro His Pro PheAsp Ser Thr Asn Pro Gly Asp Phe 210 215 220 Pro Ala Gln Tyr Ser Ala IleTyr Lys Gly Arg Thr Ala Phe Glu Asp 225 230 235 240 Thr Phe Trp Asp Trp245 16 710 PRT CELO Virus Position 28363..30495 /gene L5 /product L5fibre 1 16 Met Thr Ser Pro Leu Thr Leu Ser Gln Arg Ala Leu Ala Leu LysThr 1 5 10 15 Asp Ser Thr Leu Thr Leu Asn Thr Gln Gly Gln Leu Gly ValSer Leu 20 25 30 Thr Pro Gly Asp Gly Leu Val Leu Asn Thr Asn Gly Leu SerIle Asn 35 40 45 Ala Asp Pro Gln Thr Leu Ala Phe Asn Asn Ser Gly Ala LeuGlu Val 50 55 60 Asn Leu Asp Pro Asp Gly Pro Trp Ser Lys Thr Ala Thr GlyIle Asp 65 70 75 80 Leu Arg Leu Asp Pro Thr Thr Leu Glu Val Asp Asn TrpGlu Leu Gly 85 90 95 Val Lys Leu Asp Pro Asp Glu Ala Ile Asp Ser Gly ProAsp Gly Leu 100 105 110 Cys Leu Asn Leu Asp Glu Thr Leu Leu Leu Ala ThrAsn Ser Thr Ser 115 120 125 Gly Lys Thr Glu Leu Gly Val His Leu Asn ThrSer Gly Pro Ile Thr 130 135 140 Ala Asp Asp Gln Gly Ile Asp Leu Asp ValAsp Pro Asn Thr Met Gln 145 150 155 160 Val Asn Thr Gly Pro Ser Gly GlyMet Leu Ala Val Lys Leu Lys Ser 165 170 175 Gly Gly Gly Leu Thr Ala AspPro Asp Gly Ile Ser Val Thr Ala Thr 180 185 190 Val Ala Pro Pro Ser IleSer Ala Thr Ala Pro Leu Thr Tyr Thr Ser 195 200 205 Gly Thr Ile Ala LeuThr Thr Asp Thr Gln Thr Met Gln Val Asn Ser 210 215 220 Asn Gln Leu AlaVal Lys Leu Lys Thr Gly Gly Gly Leu Thr Ala Asp 225 230 235 240 Ala AspGly Ile Ser Val Ser Val Ala Pro Thr Pro Thr Ile Ser Ala 245 250 255 SerPro Pro Leu Thr Tyr Thr Asn Gly Gln Ile Gly Leu Ser Ile Gly 260 265 270Asp Gln Ser Leu Gln Val Ser Ser Gly Gln Leu Gln Val Lys Leu Lys 275 280285 Ser Gln Gly Gly Ile Gln Gln Ser Thr Gln Gly Leu Gly Val Ala Val 290295 300 Asp Gln Thr Leu Lys Ile Val Ser Asn Thr Leu Glu Val Asn Thr Asp305 310 315 320 Pro Ser Gly Pro Leu Thr Ser Gly Asn Asn Gly Leu Ser LeuAla Ala 325 330 335 Val Thr Pro Leu Ala Val Ser Ser Ala Gly Val Thr LeuAsn Tyr Gln 340 345 350 Ser Pro Leu Thr Val Thr Ser Asn Ser Leu Gly LeuSer Ile Ala Ala 355 360 365 Pro Leu Gln Ala Gly Ala Gln Gly Leu Thr ValAsn Thr Met Glu Pro 370 375 380 Leu Ser Ala Ser Ala Gln Gly Ile Gln LeuHis Tyr Gly Gln Gly Phe 385 390 395 400 Gln Val Val Ala Gly Thr Leu GlnLeu Leu Thr Asn Pro Pro Ile Val 405 410 415 Val Ser Ser Arg Gly Phe ThrLeu Leu Tyr Thr Pro Ala Phe Thr Val 420 425 430 Ser Asn Asn Met Leu GlyLeu Asn Val Asp Gly Thr Asp Cys Val Ala 435 440 445 Ile Ser Ser Ala GlyLeu Gln Ile Arg Lys Glu Ala Pro Leu Tyr Val 450 455 460 Thr Ser Gly SerThr Pro Ala Leu Ala Leu Lys Tyr Ser Ser Asp Phe 465 470 475 480 Thr IleThr Asn Gly Ala Leu Ala Leu Ala Asn Ser Gly Gly Gly Gly 485 490 495 SerSer Thr Pro Glu Val Ala Thr Tyr His Cys Gly Asp Asn Leu Leu 500 505 510Glu Ser Tyr Asp Ile Phe Ala Ser Leu Pro Asn Thr Asn Ala Ala Lys 515 520525 Val Ala Ala Tyr Cys Arg Leu Ala Ala Ala Gly Gly Val Val Ser Gly 530535 540 Thr Ile Gln Val Thr Ser Tyr Ala Gly Arg Trp Pro Lys Val Gly Asn545 550 555 560 Ser Val Thr Asp Gly Ile Lys Phe Ala Ile Val Val Ser ProPro Met 565 570 575 Asp Lys Asp Pro Arg Ser Asn Leu Ser Gln Trp Leu GlyAla Thr Val 580 585 590 Phe Pro Ala Gly Ala Thr Thr Ala Leu Phe Ser ProAsn Pro Tyr Gly 595 600 605 Ser Leu Asn Thr Ile Thr Thr Leu Pro Ser IleAla Ser Asp Trp Tyr 610 615 620 Val Pro Glu Ser Asn Leu Val Thr Tyr ThrLys Ile His Phe Lys Pro 625 630 635 640 Thr Gly Ser Gln Gln Leu Gln LeuAla Ser Gly Glu Leu Val Val Ala 645 650 655 Ala Ala Lys Ser Pro Val GlnThr Thr Lys Tyr Glu Leu Ile Tyr Leu 660 665 670 Gly Phe Thr Leu Lys GlnAsn Ser Ser Gly Thr Asn Phe Phe Asp Pro 675 680 685 Asn Ala Ser Ser AspLeu Ser Phe Leu Thr Pro Pro Ile Pro Phe Thr 690 695 700 Tyr Leu Gly TyrTyr Gln 705 710 17 410 PRT CELO Virus Position 30536..31768 /gene L5/product L5 fibre 2 17 Met Ala Asp Gln Lys Arg Lys Leu Ala Asp Pro AspAla Glu Ala Pro 1 5 10 15 Thr Gly Lys Met Ala Arg Ala Gly Pro Gly GluLeu Asp Leu Val Tyr 20 25 30 Pro Phe Trp Tyr Gln Val Ala Ala Pro Thr GluIle Thr Pro Pro Phe 35 40 45 Leu Asp Pro Asn Gly Pro Leu Tyr Ser Thr AspGly Leu Leu Asn Val 50 55 60 Arg Leu Thr Ala Pro Leu Val Ile Ile Arg GlnSer Asn Gly Asn Ala 65 70 75 80 Ile Gly Val Lys Thr Asp Gly Ser Ile ThrVal Asn Ala Asp Gly Ala 85 90 95 Leu Gln Ile Gly Ile Ser Thr Ala Gly ProLeu Thr Thr Thr Ala Asn 100 105 110 Gly Ile Asp Leu Asn Ile Asp Pro LysThr Leu Val Val Asp Gly Ser 115 120 125 Ser Gly Lys Asn Val Leu Gly ValLeu Leu Lys Gly Gln Gly Ala Leu 130 135 140 Gln Ser Ser Ala Gln Gly IleGly Val Ala Val Asp Glu Ser Leu Gln 145 150 155 160 Ile Val Asp Asn ThrLeu Glu Val Lys Val Asp Ala Ala Gly Pro Leu 165 170 175 Ala Val Thr AlaAla Gly Val Gly Leu Gln Tyr Asp Asn Thr Gln Phe 180 185 190 Lys Val ThrAsn Gly Thr Leu Gln Leu Tyr Gln Ala Pro Thr Ser Ser 195 200 205 Val AlaAla Phe Thr Ser Gly Thr Ile Gly Leu Ser Ser Pro Thr Gly 210 215 220 AsnPhe Val Ser Ser Ser Asn Asn Pro Phe Asn Gly Ser Tyr Phe Leu 225 230 235240 Gln Gln Ile Asn Thr Met Gly Met Leu Thr Thr Ser Leu Tyr Val Lys 245250 255 Val Asp Thr Thr Thr Met Gly Thr Arg Pro Thr Gly Ala Val Asn Glu260 265 270 Asn Ala Arg Tyr Phe Thr Val Trp Val Ser Ser Phe Leu Thr GlnCys 275 280 285 Asn Pro Ser Asn Ile Gly Gln Gly Thr Leu Glu Pro Ser AsnIle Ser 290 295 300 Met Thr Ser Phe Glu Pro Ala Arg Asn Pro Ile Ser ProPro Val Phe 305 310 315 320 Asn Met Asn Gln Asn Ile Pro Tyr Tyr Ala SerArg Phe Gly Val Leu 325 330 335 Glu Ser Tyr Arg Pro Ile Phe Thr Gly SerLeu Asn Thr Gly Ser Ile 340 345 350 Asp Val Arg Met Gln Val Thr Pro ValLeu Ala Thr Asn Asn Thr Thr 355 360 365 Tyr Asn Leu Ile Ala Phe Thr PheGln Cys Ala Ser Ala Gly Leu Phe 370 375 380 Asn Pro Thr Val Asn Gly ThrVal Ala Ile Gly Pro Val Val His Thr 385 390 395 400 Cys Pro Ala Ala ArgAla Pro Val Thr Val 405 410 18 148 PRT CELO Virus Position 33030..33476/note=ORF5 18 Met Arg Leu Pro Val Leu Pro Val His Met Lys Tyr Pro LeuPhe Asp 1 5 10 15 Val Ser Val Gly Gln Pro Thr Val Thr Gly Glu Val ThrGln Ser Leu 20 25 30 Arg His Asp Arg Pro Gln Phe Arg Arg His His His AlaGlu His Ala 35 40 45 Ser Gln Ala Asp Gly Leu Gly His Gly Ala Ala Ala ArgAsn Ser Phe 50 55 60 His His Asp Gly Gly Arg His Gly His Ala Thr Arg IleHis Glu Asn 65 70 75 80 Asn Arg Arg Pro His Lys Arg Asn Arg Arg Arg HisLeu Arg Lys Gly 85 90 95 His Leu Lys Ala His Arg Ala Glu Ser His Leu TyrGly Tyr Leu Leu 100 105 110 Arg Asn Gln Lys Ala Cys Gly Glu Lys Leu LysIle Cys Leu Pro Ala 115 120 125 Ser Lys His Pro Arg Phe Gln Val Val LeuHis Pro Arg Cys Asn Lys 130 135 140 Lys Gln Pro Thr 145 19 104 PRT CELOVirus Position 33169..33483 /note=ORF6 19 Met Leu Leu Arg Gln Thr GlyTrp Val Thr Ala Leu Leu Arg Glu Ile 1 5 10 15 Val Ser Thr Met Met ValAla Val Thr Val Thr Arg His Ala Phe Met 20 25 30 Arg Thr Thr Gly Asp ArgThr Lys Gly Thr Asp Glu Gly Thr Cys Glu 35 40 45 Lys Asp Thr Ser Lys LeuIle Glu Arg Arg Ala Ile Phe Thr Asp Ile 50 55 60 Phe Ser Ala Ile Arg LysPro Val Val Lys Asn Leu Lys Ser Val Phe 65 70 75 80 Leu Arg Ala Ser IleHis Gly Ser Lys Ser Tyr Phe Ile Pro Gly Val 85 90 95 Ile Lys Ser Asn LeuArg Glu Arg 100 20 131 PRT CELO Virus Position 35629..36024 /note= ORF720 Met Asn Ser Met Val Leu Glu Leu Arg Lys Lys Met Ser Ser Gly Pro 1 510 15 Asp Cys Val Ile Gly Arg Pro Pro His Ile Leu Pro Pro Gln Lys Gly 2025 30 Val Tyr Leu Leu Thr Asn Ile Ser Gln Leu Ile Gly Pro Val Gln Gln 3540 45 Asn Asp Arg Gly Leu Trp Arg His Asn Gly Met His Thr Gln Asn Leu 5055 60 Ser His His Phe Thr Gly Pro Phe Ile Cys Ala Val Ile Ala Arg Pro 6570 75 80 Ile Asn Lys Arg Thr His Ile Gly Ile His Val Leu Asn Gln Asn Asn85 90 95 Glu Leu Pro Ala Ile Phe Thr Ile Gln Tyr Pro Glu Pro Pro His Leu100 105 110 Thr Asp Asn Pro Gly Ala Val Arg Lys Ser Gln Lys Ser Leu IlePro 115 120 125 Pro Tyr Asn 130 21 282 PRT CELO Virus Position37391..38239 /note=ORF8 21 Met Ala Arg Asn Pro Phe Arg Met Phe Pro GlyAsp Leu Pro Tyr Tyr 1 5 10 15 Met Gly Thr Ile Ser Phe Thr Ser Val ValPro Val Asp Pro Ser Gln 20 25 30 Arg Asn Pro Thr Thr Ser Leu Arg Glu MetVal Thr Thr Gly Leu Ile 35 40 45 Phe Asn Pro Asn Leu Thr Gly Glu Gln LeuArg Glu Tyr Ser Phe Ser 50 55 60 Pro Leu Val Ser Met Gly Arg Lys Ala IlePhe Ala Asp Tyr Glu Gly 65 70 75 80 Pro Gln Arg Ile Ile His Val Thr IleArg Gly Arg Ser Ala Glu Pro 85 90 95 Lys Thr Pro Ser Glu Ala Leu Ile MetMet Glu Lys Ala Val Arg Gly 100 105 110 Ala Phe Ala Val Pro Asp Trp ValAla Arg Glu Tyr Ser Asp Pro Leu 115 120 125 Pro His Gly Ile Thr His ValGly Asp Leu Gly Phe Pro Ile Gly Ser 130 135 140 Val His Ala Leu Lys MetAla Leu Asp Thr Leu Lys Ile His Val Pro 145 150 155 160 Arg Gly Val GlyVal Pro Gly Tyr Glu Gly Leu Cys Gly Thr Thr Thr 165 170 175 Ile Lys AlaPro Arg Gln Tyr Arg Leu Leu Thr Thr Gly Val Phe Thr 180 185 190 Lys LysAsp Leu Lys Arg Thr Leu Pro Glu Pro Phe Phe Ser Arg Phe 195 200 205 PheAsn Gln Thr Pro Glu Val Cys Ala Ile Lys Thr Gly Lys Asn Pro 210 215 220Phe Ser Thr Glu Ile Trp Cys Met Thr Leu Gly Gly Asp Ser Pro Ala 225 230235 240 Pro Glu Arg Asn Glu Pro Arg Asn Pro His Ser Leu Gln Asp Trp Ala245 250 255 Arg Leu Gly Val Met Glu Thr Cys Leu Arg Met Ser Arg Arg GlyLeu 260 265 270 Gly Ser Arg His His Pro Tyr His Ser Leu 275 280 22 321PRT CELO Virus Position 40037..41002 /note=ORF9 22 Met Glu Pro Pro HisAsn Ser Pro Val Pro Phe Ser Ile Ala Lys Met 1 5 10 15 Gly Asn Pro ThrLeu Leu Leu Leu Ser Gly Leu Leu Ser Leu Thr Gln 20 25 30 Ala Ile Ser IleGly Glu His Glu Asn Lys Thr Arg His Val Ile Val 35 40 45 Trp Arg His SerSer Ser His Gln Cys Ser Asp Trp Arg Thr Val Thr 50 55 60 Glu Trp Phe ProPro Gln Lys Gly Asn Pro Val Arg Pro Pro Tyr Thr 65 70 75 80 Gln Arg ValSer Leu Asp Thr Ala Asn Asn Thr Leu Thr Val Lys Pro 85 90 95 Phe Glu ThrAsn Asn Gly Cys Trp Glu Thr Thr Ser Gln Gly Ile Asn 100 105 110 His ProPro Thr Thr Ile Gln Tyr Arg Val Trp Asn Ile Thr Thr Thr 115 120 125 ProThr Ile Gln Thr Ile Asn Ile Thr Lys Ile Thr Val Arg Glu Gly 130 135 140Glu Asp Phe Thr Leu Tyr Gly Pro Val Ser Glu Thr Met Ser Ile Ile 145 150155 160 Glu Trp Glu Phe Ile Lys Asp Val Thr Pro Gln Phe Ile Leu Gln Tyr165 170 175 Tyr Leu Ser Ile Asn Ser Thr Ile Val Tyr Ala Ser Tyr Gln GlyArg 180 185 190 Val Thr Phe Asn Pro Gly Lys Asn Thr Leu Thr Leu Lys GlyAla Lys 195 200 205 Thr Thr Asp Ser Gly Thr Tyr Lys Ser Thr Val Asn LeuAsp Gln Val 210 215 220 Ser Val His Asn Phe Arg Val Gly Val Thr Pro IleGlu Lys Lys Glu 225 230 235 240 Glu Ala Thr Ala Glu Thr Pro Ala Ser LysPro Thr Pro Ile Pro Arg 245 250 255 Val Arg Ala Asp Ala Arg Ser Thr AlaLeu Trp Val Gly Leu Ala Leu 260 265 270 Cys Ile Leu Thr Val Ile Pro AlaLeu Ile Gly Trp Tyr Phe Arg Asp 275 280 285 Arg Leu Cys Val Pro Asp ProIle Ile Glu Leu Glu Ile Pro Gly Gln 290 295 300 Pro His Val Thr Ile HisIle Leu Lys Gly Pro Asp Asp Asp Cys Glu 305 310 315 320 Thr 23 283 PRTCELO Virus Position 41002..41853 /note=ORF10 23 Met Ile Asp Lys Arg AsnLys Lys Ala Val Thr His Ile Ser Thr Cys 1 5 10 15 Leu Cys His Ser SerIle Pro Ile Tyr Gly Asp Ser Pro Phe Leu Asn 20 25 30 Thr His Arg Ala AlaMet Asp Pro Arg Pro Leu Val Leu Leu Leu Leu 35 40 45 Leu Ala Ser His IleSer Thr Phe Arg Gln Met Tyr Phe Glu Gly Glu 50 55 60 Thr Ile His Phe ProMet Gly Ile Tyr Gly Asn Glu Thr Thr Leu Tyr 65 70 75 80 Met Asn Asp IleIle Leu Glu Gly Thr Arg Ala Asn Thr Thr Thr Arg 85 90 95 Thr Ile Ser LeuThr Thr Thr Lys Lys Asn Ala Gly Thr Asn Leu Tyr 100 105 110 Thr Val IleSer Glu Thr Gly His Asn Ala Thr Tyr Leu Ile Thr Val 115 120 125 Gln ProLeu Gly Gln Ser Ile His His Ala Tyr Thr Trp Ala Gly Asn 130 135 140 ThrPhe Thr Leu Gln Gly Gln Val Phe Glu His Gly Asn Tyr Thr Arg 145 150 155160 Trp Val Arg Leu Glu Asn Ala Glu Pro Lys Leu Ile Ile Ser Trp Ala 165170 175 Leu Ser Asn Arg Thr Ile Asn Lys Gly Pro Ala Tyr Thr Ala Asn Met180 185 190 Asp Phe Asp Pro Gly Asn Asn Thr Leu Thr Leu His Pro Val LeuIle 195 200 205 Thr Asp Ala Gly Ile Phe Gln Cys Val Ile Asp Gln Gln ThrAsn Leu 210 215 220 Thr Leu Thr Ile Asn Phe Thr Val Ser Glu Asn Pro ProIle Val Ala 225 230 235 240 His Leu Asp Ile His Lys Thr Ile Ser Arg ThrIle Ala Ile Cys Ser 245 250 255 Cys Leu Leu Ile Ala Val Ile Ala Val LeuCys Cys Leu Arg Gln Leu 260 265 270 Asn Val Asn Gly Arg Gly Asn Ser GluMet Ile 275 280 24 135 PRT CELO Virus Position 41958..42365 /note= ORF1124 Met Leu Leu Leu Thr Val Val Leu Leu Val Gly Val Thr Leu Ala Ala 1 510 15 Asp His Pro Thr Leu Tyr Ala Pro Lys Gly Gly Ser Ile Glu Leu Gly 2025 30 Val Gly Ala Lys Gln Lys Gly Gln Tyr Lys Phe Glu Trp Arg Phe Gly 3540 45 Asn Leu Lys Ile Val Ile Ala Glu Met Ser Ser Thr Asn Gln Leu Glu 5055 60 Ile Lys Phe Pro Asp Asn Gly Phe Gln Asn Arg Ser Glu Phe Asn Pro 6570 75 80 Thr Lys His Asn Leu Thr Ile His Asn Ala Ser Tyr Glu Asp Ser Gly85 90 95 Thr Tyr Ser Leu His Gln Glu Glu Asn Asp Gly Thr Glu His Thr Asp100 105 110 Asn Phe Lys Val Ile Val Gln Gly Met Ser Leu Tyr Thr Tyr LeuGln 115 120 125 Tyr Ala Leu Ile Ser Pro Ile 130 135 25 1326 DNA CELOVIRUS CDS (1)..(1326) 25 atg gaa aga acc ccg aaa aga gct cat ggc ttt cgcagc acc aag cct 48 Met Glu Arg Thr Pro Lys Arg Ala His Gly Phe Arg SerThr Lys Pro 1 5 10 15 gtc aag aga acg gca gaa gtc atg atg gaa gag gaggag gaa gaa gtg 96 Val Lys Arg Thr Ala Glu Val Met Met Glu Glu Glu GluGlu Glu Val 20 25 30 gaa gtg gtc gcc ccg ggc cga ggc gcg act cgc aag aaggtc agc cgc 144 Glu Val Val Ala Pro Gly Arg Gly Ala Thr Arg Lys Lys ValSer Arg 35 40 45 cgc gag gag tcc cca tcc ccc gta agg cga gtt acc cgc cggcgg gaa 192 Arg Glu Glu Ser Pro Ser Pro Val Arg Arg Val Thr Arg Arg ArgGlu 50 55 60 acc gtt gtc gat gac gaa gaa aac gcc agc gac gag gaa tcc ccggag 240 Thr Val Val Asp Asp Glu Glu Asn Ala Ser Asp Glu Glu Ser Pro Glu65 70 75 80 gcc cct ctg tca gac ccc gtg gtc tac ggc gcg caa cgc gcc atggcc 288 Ala Pro Leu Ser Asp Pro Val Val Tyr Gly Ala Gln Arg Ala Met Ala85 90 95 acc gtc gcc agc atc tgc gaa gct ctc gac cta cag tgg cag gga gcc336 Thr Val Ala Ser Ile Cys Glu Ala Leu Asp Leu Gln Trp Gln Gly Ala 100105 110 agc gtg cgc ccc gac gac tcc att tgg acc aaa atg ggg ggt aca tac384 Ser Val Arg Pro Asp Asp Ser Ile Trp Thr Lys Met Gly Gly Thr Tyr 115120 125 gtt cgc aaa aag cat ccc gaa ttt cgc ctg acc ttt tct agc tac gac432 Val Arg Lys Lys His Pro Glu Phe Arg Leu Thr Phe Ser Ser Tyr Asp 130135 140 tct ttc aac gct cag gta ggg cgg ttc ctg gca gcc gtt atc tac agc480 Ser Phe Asn Ala Gln Val Gly Arg Phe Leu Ala Ala Val Ile Tyr Ser 145150 155 160 cgc gcg ggt ctg gag ccc aag ttc gtg ccc gga ggg gcg cac gtttgg 528 Arg Ala Gly Leu Glu Pro Lys Phe Val Pro Gly Gly Ala His Val Trp165 170 175 cgc cat ggc tgg ttc cca gcg ctc cag gag ccc ttc ccg aaa tgcatg 576 Arg His Gly Trp Phe Pro Ala Leu Gln Glu Pro Phe Pro Lys Cys Met180 185 190 cac ggt gtg gac atg gtg acg aaa cct cgt acc gtg gag ttg aacccg 624 His Gly Val Asp Met Val Thr Lys Pro Arg Thr Val Glu Leu Asn Pro195 200 205 tct agc gag gcg gga aag agg gct ctg gcc gaa cag aac ggc gtaatc 672 Ser Ser Glu Ala Gly Lys Arg Ala Leu Ala Glu Gln Asn Gly Val Ile210 215 220 gag aag aac cgg ttt gga cga cag gtg gtg gtg ctc agg ttc gacgcg 720 Glu Lys Asn Arg Phe Gly Arg Gln Val Val Val Leu Arg Phe Asp Ala225 230 235 240 aac gcg gtg tgc tac aag gat cag gag cac agc ggc ttc cctcat ccc 768 Asn Ala Val Cys Tyr Lys Asp Gln Glu His Ser Gly Phe Pro HisPro 245 250 255 cac gcg cac ggc agt tgc gcc atg gtc ttt tcc gac gcc gccaag gcg 816 His Ala His Gly Ser Cys Ala Met Val Phe Ser Asp Ala Ala LysAla 260 265 270 gtc agc gcg atg cgt cac gac ata gac tgg acg aag gcg ctttac ccc 864 Val Ser Ala Met Arg His Asp Ile Asp Trp Thr Lys Ala Leu TyrPro 275 280 285 aac gcg gac aag cgc cgg gca gag gaa tgt gtc ctc atc tcaacc aat 912 Asn Ala Asp Lys Arg Arg Ala Glu Glu Cys Val Leu Ile Ser ThrAsn 290 295 300 tgc aac tgc aac tac gcc tcc gat cga gcc att tca ggg agacag ttc 960 Cys Asn Cys Asn Tyr Ala Ser Asp Arg Ala Ile Ser Gly Arg GlnPhe 305 310 315 320 tgt aaa atg act cct tat aag ctc aac ggc aca gac gacatt act cgc 1008 Cys Lys Met Thr Pro Tyr Lys Leu Asn Gly Thr Asp Asp IleThr Arg 325 330 335 gac atg gtc gag agc agg ccc gat atg aag gct cac aagaaa aac ccg 1056 Asp Met Val Glu Ser Arg Pro Asp Met Lys Ala His Lys LysAsn Pro 340 345 350 cat acc atg gtg ttc acc tgc tgc aac ccg cag gcg gcgtcg ggc gga 1104 His Thr Met Val Phe Thr Cys Cys Asn Pro Gln Ala Ala SerGly Gly 355 360 365 gca ggc cgc ggt ctg aag aag acc gaa aaa acc tgc gcctgg cgt ctg 1152 Ala Gly Arg Gly Leu Lys Lys Thr Glu Lys Thr Cys Ala TrpArg Leu 370 375 380 tcg gcc atg gat ctg cgc tac gcg tac gtc ttt gct acggag ctg ttt 1200 Ser Ala Met Asp Leu Arg Tyr Ala Tyr Val Phe Ala Thr GluLeu Phe 385 390 395 400 act gcc gtg atg ggt tct tca gag ccc aca cat gtgcct gag ttc cgt 1248 Thr Ala Val Met Gly Ser Ser Glu Pro Thr His Val ProGlu Phe Arg 405 410 415 tgg aac gag tcg tac gcc ttt aaa acg gag gtg ttggcg cca gtc tcg 1296 Trp Asn Glu Ser Tyr Ala Phe Lys Thr Glu Val Leu AlaPro Val Ser 420 425 430 ccc atc gcc agt gac gac ccg ttc gct taa 1326 ProIle Ala Ser Asp Asp Pro Phe Ala 435 440 26 441 PRT CELO VIRUS Position21899..23224/Product E2a DBP 26 Met Glu Arg Thr Pro Lys Arg Ala His GlyPhe Arg Ser Thr Lys Pro 1 5 10 15 Val Lys Arg Thr Ala Glu Val Met MetGlu Glu Glu Glu Glu Glu Val 20 25 30 Glu Val Val Ala Pro Gly Arg Gly AlaThr Arg Lys Lys Val Ser Arg 35 40 45 Arg Glu Glu Ser Pro Ser Pro Val ArgArg Val Thr Arg Arg Arg Glu 50 55 60 Thr Val Val Asp Asp Glu Glu Asn AlaSer Asp Glu Glu Ser Pro Glu 65 70 75 80 Ala Pro Leu Ser Asp Pro Val ValTyr Gly Ala Gln Arg Ala Met Ala 85 90 95 Thr Val Ala Ser Ile Cys Glu AlaLeu Asp Leu Gln Trp Gln Gly Ala 100 105 110 Ser Val Arg Pro Asp Asp SerIle Trp Thr Lys Met Gly Gly Thr Tyr 115 120 125 Val Arg Lys Lys His ProGlu Phe Arg Leu Thr Phe Ser Ser Tyr Asp 130 135 140 Ser Phe Asn Ala GlnVal Gly Arg Phe Leu Ala Ala Val Ile Tyr Ser 145 150 155 160 Arg Ala GlyLeu Glu Pro Lys Phe Val Pro Gly Gly Ala His Val Trp 165 170 175 Arg HisGly Trp Phe Pro Ala Leu Gln Glu Pro Phe Pro Lys Cys Met 180 185 190 HisGly Val Asp Met Val Thr Lys Pro Arg Thr Val Glu Leu Asn Pro 195 200 205Ser Ser Glu Ala Gly Lys Arg Ala Leu Ala Glu Gln Asn Gly Val Ile 210 215220 Glu Lys Asn Arg Phe Gly Arg Gln Val Val Val Leu Arg Phe Asp Ala 225230 235 240 Asn Ala Val Cys Tyr Lys Asp Gln Glu His Ser Gly Phe Pro HisPro 245 250 255 His Ala His Gly Ser Cys Ala Met Val Phe Ser Asp Ala AlaLys Ala 260 265 270 Val Ser Ala Met Arg His Asp Ile Asp Trp Thr Lys AlaLeu Tyr Pro 275 280 285 Asn Ala Asp Lys Arg Arg Ala Glu Glu Cys Val LeuIle Ser Thr Asn 290 295 300 Cys Asn Cys Asn Tyr Ala Ser Asp Arg Ala IleSer Gly Arg Gln Phe 305 310 315 320 Cys Lys Met Thr Pro Tyr Lys Leu AsnGly Thr Asp Asp Ile Thr Arg 325 330 335 Asp Met Val Glu Ser Arg Pro AspMet Lys Ala His Lys Lys Asn Pro 340 345 350 His Thr Met Val Phe Thr CysCys Asn Pro Gln Ala Ala Ser Gly Gly 355 360 365 Ala Gly Arg Gly Leu LysLys Thr Glu Lys Thr Cys Ala Trp Arg Leu 370 375 380 Ser Ala Met Asp LeuArg Tyr Ala Tyr Val Phe Ala Thr Glu Leu Phe 385 390 395 400 Thr Ala ValMet Gly Ser Ser Glu Pro Thr His Val Pro Glu Phe Arg 405 410 415 Trp AsnGlu Ser Tyr Ala Phe Lys Thr Glu Val Leu Ala Pro Val Ser 420 425 430 ProIle Ala Ser Asp Asp Pro Phe Ala 435 440 27 3366 DNA CELO VIRUS CDS(1)..(3366) 27 atg ctc atc gcc aaa aac gtc acc gga gaa tgg gtc tgg atcacc agc 48 Met Leu Ile Ala Lys Asn Val Thr Gly Glu Trp Val Trp Ile ThrSer 1 5 10 15 cgc act ccg gtt caa cag tgt ccc acc tgc ggc cga cac tgggtc aga 96 Arg Thr Pro Val Gln Gln Cys Pro Thr Cys Gly Arg His Trp ValArg 20 25 30 cga cac tcg tgc aac gaa cgc cgc tct gcc ttc tac tac cac gccgtc 144 Arg His Ser Cys Asn Glu Arg Arg Ser Ala Phe Tyr Tyr His Ala Val35 40 45 cag gga tcg ggc agc gat ttg tgg cag cac gtc cac ttc tcc tgt cca192 Gln Gly Ser Gly Ser Asp Leu Trp Gln His Val His Phe Ser Cys Pro 5055 60 gcc caa cac ccc cac ata cgt cag ttg tac atc acc tac gat atc gag240 Ala Gln His Pro His Ile Arg Gln Leu Tyr Ile Thr Tyr Asp Ile Glu 6570 75 80 acg tat acc gtg ttc gaa aag aaa ggc aag cgc atg cat ccg ttt atg288 Thr Tyr Thr Val Phe Glu Lys Lys Gly Lys Arg Met His Pro Phe Met 8590 95 ttg tgc ttc atg ctc agc gga gac ccc cag ctg gtc tcc cgc gcc gaa336 Leu Cys Phe Met Leu Ser Gly Asp Pro Gln Leu Val Ser Arg Ala Glu 100105 110 cgc tta gca cgg cag gac gac cgt ctc aaa gcc ctc gac gaa ggc ttc384 Arg Leu Ala Arg Gln Asp Asp Arg Leu Lys Ala Leu Asp Glu Gly Phe 115120 125 tat tgg cta gac agc cat ccg ggc gag gtt gcc aga agg ttt cgc aac432 Tyr Trp Leu Asp Ser His Pro Gly Glu Val Ala Arg Arg Phe Arg Asn 130135 140 ttc agg tcc cgt ctg caa ata gaa ttt gcc caa aat cta gtc gac cgc480 Phe Arg Ser Arg Leu Gln Ile Glu Phe Ala Gln Asn Leu Val Asp Arg 145150 155 160 tac gcg gct gcc aac cga gat tat tgc gac cag cta gtc aag gacgga 528 Tyr Ala Ala Ala Asn Arg Asp Tyr Cys Asp Gln Leu Val Lys Asp Gly165 170 175 aag tac ggc tcc gtt cac aaa ata ccg tac gag ctc ttc gag aaaccc 576 Lys Tyr Gly Ser Val His Lys Ile Pro Tyr Glu Leu Phe Glu Lys Pro180 185 190 acc tcc ccc ctc tcc ctc ccg gat aac ttt tat tcc gta gac atcgta 624 Thr Ser Pro Leu Ser Leu Pro Asp Asn Phe Tyr Ser Val Asp Ile Val195 200 205 gtg cta ggt cac aac ata tgt aag ttc gat gaa ctc ctc tta gccacg 672 Val Leu Gly His Asn Ile Cys Lys Phe Asp Glu Leu Leu Leu Ala Thr210 215 220 gaa ctc gtc gag cgc agg gac cta ttc ccg gaa gcg tgc aaa tgtgat 720 Glu Leu Val Glu Arg Arg Asp Leu Phe Pro Glu Ala Cys Lys Cys Asp225 230 235 240 cga tcc ttc atg cct cgc gtc ggt cgc ctt ctg ttc aat gatatc att 768 Arg Ser Phe Met Pro Arg Val Gly Arg Leu Leu Phe Asn Asp IleIle 245 250 255 ttc cgc atg cca aac ccc aac tac gtg aag aaa gac gcc tcccgc gta 816 Phe Arg Met Pro Asn Pro Asn Tyr Val Lys Lys Asp Ala Ser ArgVal 260 265 270 gaa cgc tgg tct cgc ggg atc gtg tcc cat cag gat gcg cgctcg gta 864 Glu Arg Trp Ser Arg Gly Ile Val Ser His Gln Asp Ala Arg SerVal 275 280 285 ttt gtg cgg ttc atg gtg cga gac act cta cag ctc acc agcggg gcc 912 Phe Val Arg Phe Met Val Arg Asp Thr Leu Gln Leu Thr Ser GlyAla 290 295 300 aaa ctc tcc aaa gcc gcg gca gcc tac gcg cta gac ctc tgcaag gga 960 Lys Leu Ser Lys Ala Ala Ala Ala Tyr Ala Leu Asp Leu Cys LysGly 305 310 315 320 cat tgc cca tac gag gcc atc aac gaa ttc att tcc acgggg cgc ttt 1008 His Cys Pro Tyr Glu Ala Ile Asn Glu Phe Ile Ser Thr GlyArg Phe 325 330 335 cac gcg gac gcc gac ggc ttt cct gtc gaa agg tac tgggaa gac cca 1056 His Ala Asp Ala Asp Gly Phe Pro Val Glu Arg Tyr Trp GluAsp Pro 340 345 350 tcc gtc atc gct gaa cag aag aat cta tgg cag aaa gaacac ccg ggc 1104 Ser Val Ile Ala Glu Gln Lys Asn Leu Trp Gln Lys Glu HisPro Gly 355 360 365 cag cag tac gac atc gtc caa gcg tgc ctc gaa tac tgcatg cag gac 1152 Gln Gln Tyr Asp Ile Val Gln Ala Cys Leu Glu Tyr Cys MetGln Asp 370 375 380 gtc cgc gtc acc caa aag ctg gcc cac acg tta cac gacagc tac gac 1200 Val Arg Val Thr Gln Lys Leu Ala His Thr Leu His Asp SerTyr Asp 385 390 395 400 gcc tat ttc caa cga gaa cta ggg atg gaa ggc catttt aac atc ttc 1248 Ala Tyr Phe Gln Arg Glu Leu Gly Met Glu Gly His PheAsn Ile Phe 405 410 415 gtg cgg ccc acc atc ccc agc aac act cat gcc ttttgg aag caa ctt 1296 Val Arg Pro Thr Ile Pro Ser Asn Thr His Ala Phe TrpLys Gln Leu 420 425 430 acc ttt tcc aat tac gtc cgc gaa cag cgt gcg acatgc cct ccc tcc 1344 Thr Phe Ser Asn Tyr Val Arg Glu Gln Arg Ala Thr CysPro Pro Ser 435 440 445 gtc ccc gaa ccc ccc aaa aag aaa ggt cga acc aaaaag aaa aaa caa 1392 Val Pro Glu Pro Pro Lys Lys Lys Gly Arg Thr Lys LysLys Lys Gln 450 455 460 ccc tcc ccc gac tac gtg gcc gaa gtc tac gcc ccccac cgc ccc atg 1440 Pro Ser Pro Asp Tyr Val Ala Glu Val Tyr Ala Pro HisArg Pro Met 465 470 475 480 ttc aaa tac ata cgc caa gcg ctc cgc ggc ggacga tgc tac ccc aac 1488 Phe Lys Tyr Ile Arg Gln Ala Leu Arg Gly Gly ArgCys Tyr Pro Asn 485 490 495 gtg ctc gga cct tac ctg aaa ccc gtc tac gtcttt gac atc tgc ggc 1536 Val Leu Gly Pro Tyr Leu Lys Pro Val Tyr Val PheAsp Ile Cys Gly 500 505 510 atg tac gct tcc gcc ctc acc cac ccc atg ccccac gga atg ccc cta 1584 Met Tyr Ala Ser Ala Leu Thr His Pro Met Pro HisGly Met Pro Leu 515 520 525 gat cca aaa ttt acc gcg cag cac gtg gag gagctc aac cgg ctg ctg 1632 Asp Pro Lys Phe Thr Ala Gln His Val Glu Glu LeuAsn Arg Leu Leu 530 535 540 acc aac gaa tcg cat ctg agc tac ttc gat gcgcgt atc aag cct tcc 1680 Thr Asn Glu Ser His Leu Ser Tyr Phe Asp Ala ArgIle Lys Pro Ser 545 550 555 560 atc ctg aaa ata gaa gcc tac cct ccc ccgccc gaa atg tta gac cca 1728 Ile Leu Lys Ile Glu Ala Tyr Pro Pro Pro ProGlu Met Leu Asp Pro 565 570 575 ctc cct ccc atc tgc tcc cgg agg gga ggcaga ctg gtc tgg acc aac 1776 Leu Pro Pro Ile Cys Ser Arg Arg Gly Gly ArgLeu Val Trp Thr Asn 580 585 590 gag gct ctc tac gac gag gtg gtc acc gtcata gat atc ctc acg ctg 1824 Glu Ala Leu Tyr Asp Glu Val Val Thr Val IleAsp Ile Leu Thr Leu 595 600 605 cac aac cgg gga tgg cga gtc cag gtc ctccat gac gag atg aac att 1872 His Asn Arg Gly Trp Arg Val Gln Val Leu HisAsp Glu Met Asn Ile 610 615 620 gtt ttt ccg gaa tgg aaa acg cta tgt gccgac tac gtc acg aaa aac 1920 Val Phe Pro Glu Trp Lys Thr Leu Cys Ala AspTyr Val Thr Lys Asn 625 630 635 640 atc ctc gcc aaa gaa aaa gcc gat cgcgag aag aac gaa gtg att cga 1968 Ile Leu Ala Lys Glu Lys Ala Asp Arg GluLys Asn Glu Val Ile Arg 645 650 655 tcc atc tcc aaa atg ctg agc aac gcgctg tac ggt gcg ttt gcc acc 2016 Ser Ile Ser Lys Met Leu Ser Asn Ala LeuTyr Gly Ala Phe Ala Thr 660 665 670 aac atg gac acc acg cgc atc atc tttgaa cag gac ctc tcg gaa gca 2064 Asn Met Asp Thr Thr Arg Ile Ile Phe GluGln Asp Leu Ser Glu Ala 675 680 685 gat aag aaa aac atc tac gaa ggc actgaa atc gtc aaa cac gtc acg 2112 Asp Lys Lys Asn Ile Tyr Glu Gly Thr GluIle Val Lys His Val Thr 690 695 700 ctg ctc aat gac gac tcg ttc aac ggaacg gaa gtc acc ctc gaa aac 2160 Leu Leu Asn Asp Asp Ser Phe Asn Gly ThrGlu Val Thr Leu Glu Asn 705 710 715 720 gcg cct aac ccc ttc agt gag gagagt cta cga caa cag ttc cgc tac 2208 Ala Pro Asn Pro Phe Ser Glu Glu SerLeu Arg Gln Gln Phe Arg Tyr 725 730 735 gca gac gac ccc gaa cag gaa gagccc gaa gca gaa gag gat ggg gaa 2256 Ala Asp Asp Pro Glu Gln Glu Glu ProGlu Ala Glu Glu Asp Gly Glu 740 745 750 gaa gaa gga gac gac agc gat cgcgag agt gcc cgt aag ccg aaa aac 2304 Glu Glu Gly Asp Asp Ser Asp Arg GluSer Ala Arg Lys Pro Lys Asn 755 760 765 gca ctt acc gaa gac gat cct ctcgtc gcc gta gac ctg gaa gtc gag 2352 Ala Leu Thr Glu Asp Asp Pro Leu ValAla Val Asp Leu Glu Val Glu 770 775 780 gcg acc ctc gcg acg ggc cct tatata ccc gag ggg gag cta agc tcc 2400 Ala Thr Leu Ala Thr Gly Pro Tyr IlePro Glu Gly Glu Leu Ser Ser 785 790 795 800 gcc cac tac gct cgc gct aacgag acc cgg ttt aaa cct atg cgt ctc 2448 Ala His Tyr Ala Arg Ala Asn GluThr Arg Phe Lys Pro Met Arg Leu 805 810 815 ctc gaa gcc aca cca gaa gcccta acc gtg ctc cat ctg gaa agc ctg 2496 Leu Glu Ala Thr Pro Glu Ala LeuThr Val Leu His Leu Glu Ser Leu 820 825 830 gac aag cag gtg gca aac aaaaga tac gcc acg caa atc gcc tgc ttc 2544 Asp Lys Gln Val Ala Asn Lys ArgTyr Ala Thr Gln Ile Ala Cys Phe 835 840 845 gtg ctg ggc tgg tcg agg gccttc ttc agc gag tgg tgt gac atc ctg 2592 Val Leu Gly Trp Ser Arg Ala PhePhe Ser Glu Trp Cys Asp Ile Leu 850 855 860 tac gga ccg gac aga gga gtgcac atc ctg cga agg gag gag ccg cgc 2640 Tyr Gly Pro Asp Arg Gly Val HisIle Leu Arg Arg Glu Glu Pro Arg 865 870 875 880 agc ctc tat ggc gat accgac agc ctg ttc gtc aca gaa aca ggc tat 2688 Ser Leu Tyr Gly Asp Thr AspSer Leu Phe Val Thr Glu Thr Gly Tyr 885 890 895 cat cgc atg aaa agc cgcggc gcg cac cga atc aaa aca gaa tcc act 2736 His Arg Met Lys Ser Arg GlyAla His Arg Ile Lys Thr Glu Ser Thr 900 905 910 cga ctg act ttc gat ccagaa aat ccc ggc ctc tac tgg gcc tgc gat 2784 Arg Leu Thr Phe Asp Pro GluAsn Pro Gly Leu Tyr Trp Ala Cys Asp 915 920 925 tgc gac atc aag tgc aaagcc tgc gga agt gac acg tac agc tcg gaa 2832 Cys Asp Ile Lys Cys Lys AlaCys Gly Ser Asp Thr Tyr Ser Ser Glu 930 935 940 acc atc ttc cta gcg ccaaaa ctg tac gga ctg aaa aac tca atc tgc 2880 Thr Ile Phe Leu Ala Pro LysLeu Tyr Gly Leu Lys Asn Ser Ile Cys 945 950 955 960 gtc aac gaa cag tgccgc acg gta gga ccc ggg aaa atc aga tcg aag 2928 Val Asn Glu Gln Cys ArgThr Val Gly Pro Gly Lys Ile Arg Ser Lys 965 970 975 gga cac agg cag tccgaa ctc atc tac gac acg ctg ctg cgc tgt tgg 2976 Gly His Arg Gln Ser GluLeu Ile Tyr Asp Thr Leu Leu Arg Cys Trp 980 985 990 cgt aga cac gag gacgtg caa ttc gga gcg cag agc aac atc cca gag 3024 Arg Arg His Glu Asp ValGln Phe Gly Ala Gln Ser Asn Ile Pro Glu 995 1000 1005 cta cac acg cggaga acc atc ttt aaa acc acg ctt ctg aac aag gtc 3072 Leu His Thr Arg ArgThr Ile Phe Lys Thr Thr Leu Leu Asn Lys Val 1010 1015 1020 agt cgc tacgac cct ttc acc att cac aac gag cag ctc acg cga gtg 3120 Ser Arg Tyr AspPro Phe Thr Ile His Asn Glu Gln Leu Thr Arg Val 1025 1030 1035 1040 ctgcgt ccg tgg aag gac ctc acc cta tac gag cac ggg gac tac ctg 3168 Leu ArgPro Trp Lys Asp Leu Thr Leu Tyr Glu His Gly Asp Tyr Leu 1045 1050 1055tac ccc tac gac aat gag cac cca aat ccc cgc acg aca gga gac gta 3216 TyrPro Tyr Asp Asn Glu His Pro Asn Pro Arg Thr Thr Gly Asp Val 1060 10651070 cga ccc gtc cca atc gtc ggg cac gaa gac ccc ctc gca ccc cta cga3264 Arg Pro Val Pro Ile Val Gly His Glu Asp Pro Leu Ala Pro Leu Arg1075 1080 1085 tgg gaa ccc tac gcg ttc cta tcc gaa gag gaa tgc ggg caagtt cac 3312 Trp Glu Pro Tyr Ala Phe Leu Ser Glu Glu Glu Cys Gly Gln ValHis 1090 1095 1100 gac cta ctc ttc gca gat gat agc tcc cag gaa gcg gaaagc ctg gga 3360 Asp Leu Leu Phe Ala Asp Asp Ser Ser Gln Glu Ala Glu SerLeu Gly 1105 1110 1115 1120 gta tga 3366 Val 28 1121 PRT CELO VIRUSPosition 6501..9866/Product E2b pol 28 Met Leu Ile Ala Lys Asn Val ThrGly Glu Trp Val Trp Ile Thr Ser 1 5 10 15 Arg Thr Pro Val Gln Gln CysPro Thr Cys Gly Arg His Trp Val Arg 20 25 30 Arg His Ser Cys Asn Glu ArgArg Ser Ala Phe Tyr Tyr His Ala Val 35 40 45 Gln Gly Ser Gly Ser Asp LeuTrp Gln His Val His Phe Ser Cys Pro 50 55 60 Ala Gln His Pro His Ile ArgGln Leu Tyr Ile Thr Tyr Asp Ile Glu 65 70 75 80 Thr Tyr Thr Val Phe GluLys Lys Gly Lys Arg Met His Pro Phe Met 85 90 95 Leu Cys Phe Met Leu SerGly Asp Pro Gln Leu Val Ser Arg Ala Glu 100 105 110 Arg Leu Ala Arg GlnAsp Asp Arg Leu Lys Ala Leu Asp Glu Gly Phe 115 120 125 Tyr Trp Leu AspSer His Pro Gly Glu Val Ala Arg Arg Phe Arg Asn 130 135 140 Phe Arg SerArg Leu Gln Ile Glu Phe Ala Gln Asn Leu Val Asp Arg 145 150 155 160 TyrAla Ala Ala Asn Arg Asp Tyr Cys Asp Gln Leu Val Lys Asp Gly 165 170 175Lys Tyr Gly Ser Val His Lys Ile Pro Tyr Glu Leu Phe Glu Lys Pro 180 185190 Thr Ser Pro Leu Ser Leu Pro Asp Asn Phe Tyr Ser Val Asp Ile Val 195200 205 Val Leu Gly His Asn Ile Cys Lys Phe Asp Glu Leu Leu Leu Ala Thr210 215 220 Glu Leu Val Glu Arg Arg Asp Leu Phe Pro Glu Ala Cys Lys CysAsp 225 230 235 240 Arg Ser Phe Met Pro Arg Val Gly Arg Leu Leu Phe AsnAsp Ile Ile 245 250 255 Phe Arg Met Pro Asn Pro Asn Tyr Val Lys Lys AspAla Ser Arg Val 260 265 270 Glu Arg Trp Ser Arg Gly Ile Val Ser His GlnAsp Ala Arg Ser Val 275 280 285 Phe Val Arg Phe Met Val Arg Asp Thr LeuGln Leu Thr Ser Gly Ala 290 295 300 Lys Leu Ser Lys Ala Ala Ala Ala TyrAla Leu Asp Leu Cys Lys Gly 305 310 315 320 His Cys Pro Tyr Glu Ala IleAsn Glu Phe Ile Ser Thr Gly Arg Phe 325 330 335 His Ala Asp Ala Asp GlyPhe Pro Val Glu Arg Tyr Trp Glu Asp Pro 340 345 350 Ser Val Ile Ala GluGln Lys Asn Leu Trp Gln Lys Glu His Pro Gly 355 360 365 Gln Gln Tyr AspIle Val Gln Ala Cys Leu Glu Tyr Cys Met Gln Asp 370 375 380 Val Arg ValThr Gln Lys Leu Ala His Thr Leu His Asp Ser Tyr Asp 385 390 395 400 AlaTyr Phe Gln Arg Glu Leu Gly Met Glu Gly His Phe Asn Ile Phe 405 410 415Val Arg Pro Thr Ile Pro Ser Asn Thr His Ala Phe Trp Lys Gln Leu 420 425430 Thr Phe Ser Asn Tyr Val Arg Glu Gln Arg Ala Thr Cys Pro Pro Ser 435440 445 Val Pro Glu Pro Pro Lys Lys Lys Gly Arg Thr Lys Lys Lys Lys Gln450 455 460 Pro Ser Pro Asp Tyr Val Ala Glu Val Tyr Ala Pro His Arg ProMet 465 470 475 480 Phe Lys Tyr Ile Arg Gln Ala Leu Arg Gly Gly Arg CysTyr Pro Asn 485 490 495 Val Leu Gly Pro Tyr Leu Lys Pro Val Tyr Val PheAsp Ile Cys Gly 500 505 510 Met Tyr Ala Ser Ala Leu Thr His Pro Met ProHis Gly Met Pro Leu 515 520 525 Asp Pro Lys Phe Thr Ala Gln His Val GluGlu Leu Asn Arg Leu Leu 530 535 540 Thr Asn Glu Ser His Leu Ser Tyr PheAsp Ala Arg Ile Lys Pro Ser 545 550 555 560 Ile Leu Lys Ile Glu Ala TyrPro Pro Pro Pro Glu Met Leu Asp Pro 565 570 575 Leu Pro Pro Ile Cys SerArg Arg Gly Gly Arg Leu Val Trp Thr Asn 580 585 590 Glu Ala Leu Tyr AspGlu Val Val Thr Val Ile Asp Ile Leu Thr Leu 595 600 605 His Asn Arg GlyTrp Arg Val Gln Val Leu His Asp Glu Met Asn Ile 610 615 620 Val Phe ProGlu Trp Lys Thr Leu Cys Ala Asp Tyr Val Thr Lys Asn 625 630 635 640 IleLeu Ala Lys Glu Lys Ala Asp Arg Glu Lys Asn Glu Val Ile Arg 645 650 655Ser Ile Ser Lys Met Leu Ser Asn Ala Leu Tyr Gly Ala Phe Ala Thr 660 665670 Asn Met Asp Thr Thr Arg Ile Ile Phe Glu Gln Asp Leu Ser Glu Ala 675680 685 Asp Lys Lys Asn Ile Tyr Glu Gly Thr Glu Ile Val Lys His Val Thr690 695 700 Leu Leu Asn Asp Asp Ser Phe Asn Gly Thr Glu Val Thr Leu GluAsn 705 710 715 720 Ala Pro Asn Pro Phe Ser Glu Glu Ser Leu Arg Gln GlnPhe Arg Tyr 725 730 735 Ala Asp Asp Pro Glu Gln Glu Glu Pro Glu Ala GluGlu Asp Gly Glu 740 745 750 Glu Glu Gly Asp Asp Ser Asp Arg Glu Ser AlaArg Lys Pro Lys Asn 755 760 765 Ala Leu Thr Glu Asp Asp Pro Leu Val AlaVal Asp Leu Glu Val Glu 770 775 780 Ala Thr Leu Ala Thr Gly Pro Tyr IlePro Glu Gly Glu Leu Ser Ser 785 790 795 800 Ala His Tyr Ala Arg Ala AsnGlu Thr Arg Phe Lys Pro Met Arg Leu 805 810 815 Leu Glu Ala Thr Pro GluAla Leu Thr Val Leu His Leu Glu Ser Leu 820 825 830 Asp Lys Gln Val AlaAsn Lys Arg Tyr Ala Thr Gln Ile Ala Cys Phe 835 840 845 Val Leu Gly TrpSer Arg Ala Phe Phe Ser Glu Trp Cys Asp Ile Leu 850 855 860 Tyr Gly ProAsp Arg Gly Val His Ile Leu Arg Arg Glu Glu Pro Arg 865 870 875 880 SerLeu Tyr Gly Asp Thr Asp Ser Leu Phe Val Thr Glu Thr Gly Tyr 885 890 895His Arg Met Lys Ser Arg Gly Ala His Arg Ile Lys Thr Glu Ser Thr 900 905910 Arg Leu Thr Phe Asp Pro Glu Asn Pro Gly Leu Tyr Trp Ala Cys Asp 915920 925 Cys Asp Ile Lys Cys Lys Ala Cys Gly Ser Asp Thr Tyr Ser Ser Glu930 935 940 Thr Ile Phe Leu Ala Pro Lys Leu Tyr Gly Leu Lys Asn Ser IleCys 945 950 955 960 Val Asn Glu Gln Cys Arg Thr Val Gly Pro Gly Lys IleArg Ser Lys 965 970 975 Gly His Arg Gln Ser Glu Leu Ile Tyr Asp Thr LeuLeu Arg Cys Trp 980 985 990 Arg Arg His Glu Asp Val Gln Phe Gly Ala GlnSer Asn Ile Pro Glu 995 1000 1005 Leu His Thr Arg Arg Thr Ile Phe LysThr Thr Leu Leu Asn Lys Val 1010 1015 1020 Ser Arg Tyr Asp Pro Phe ThrIle His Asn Glu Gln Leu Thr Arg Val 1025 1030 1035 1040 Leu Arg Pro TrpLys Asp Leu Thr Leu Tyr Glu His Gly Asp Tyr Leu 1045 1050 1055 Tyr ProTyr Asp Asn Glu His Pro Asn Pro Arg Thr Thr Gly Asp Val 1060 1065 1070Arg Pro Val Pro Ile Val Gly His Glu Asp Pro Leu Ala Pro Leu Arg 10751080 1085 Trp Glu Pro Tyr Ala Phe Leu Ser Glu Glu Glu Cys Gly Gln ValHis 1090 1095 1100 Asp Leu Leu Phe Ala Asp Asp Ser Ser Gln Glu Ala GluSer Leu Gly 1105 1110 1115 1120 Val 29 1728 DNA CELO VIRUS CDS(1)..(1728) 29 atg caa ctc cga gac ctc gcg ccg cga tcg ccg aac gtc gccgcg ccg 48 Met Gln Leu Arg Asp Leu Ala Pro Arg Ser Pro Asn Val Ala AlaPro 1 5 10 15 ccc tac aac gga ttg ccg ccg ccg cac ctt ctc ctc ggg taccaa gct 96 Pro Tyr Asn Gly Leu Pro Pro Pro His Leu Leu Leu Gly Tyr GlnAla 20 25 30 atg cac cgc gcg ctc aac gat tac ctt ttc gac aac cgc gtt tttatg 144 Met His Arg Ala Leu Asn Asp Tyr Leu Phe Asp Asn Arg Val Phe Met35 40 45 cag ata ggt tac gat agc cca ccc caa aga ccc aga cgc ctc ttt tgg192 Gln Ile Gly Tyr Asp Ser Pro Pro Gln Arg Pro Arg Arg Leu Phe Trp 5055 60 acc tgt ctg acc gac tgc tcc tac gcc gtc aat gta ggg cag tac atg240 Thr Cys Leu Thr Asp Cys Ser Tyr Ala Val Asn Val Gly Gln Tyr Met 6570 75 80 cga ttt ctc gat ctc gac aac ttt cac ggt acg ttc acg cag atg cac288 Arg Phe Leu Asp Leu Asp Asn Phe His Gly Thr Phe Thr Gln Met His 8590 95 aac gcc gta ctc atg gac cgc gtg gcc gcg gac atg ggc cgg gcg cat336 Asn Ala Val Leu Met Asp Arg Val Ala Ala Asp Met Gly Arg Ala His 100105 110 ctg cga ggt agg gga atc gac gta ggc cgt cac gga caa gtg ttg ccg384 Leu Arg Gly Arg Gly Ile Asp Val Gly Arg His Gly Gln Val Leu Pro 115120 125 cag ctc gac gcc gaa cac cac agc cta ctg tcg ggc aac gga gcg ggt432 Gln Leu Asp Ala Glu His His Ser Leu Leu Ser Gly Asn Gly Ala Gly 130135 140 ggc ttg caa gaa ggc gtc ctc atg cga acg gcc tct gcc gcc gac gcc480 Gly Leu Gln Glu Gly Val Leu Met Arg Thr Ala Ser Ala Ala Asp Ala 145150 155 160 gaa ctg ctc gcc gcc atc cgc caa cta aga gtc gcc ctc tgc cactat 528 Glu Leu Leu Ala Ala Ile Arg Gln Leu Arg Val Ala Leu Cys His Tyr165 170 175 cta ttc tgc tac gca tat gat cta ttt caa acg gaa gaa aga tatcgg 576 Leu Phe Cys Tyr Ala Tyr Asp Leu Phe Gln Thr Glu Glu Arg Tyr Arg180 185 190 ttc tta cct gga tcc gat gtg ttc ctt gaa cca aac tgg ctc tcctac 624 Phe Leu Pro Gly Ser Asp Val Phe Leu Glu Pro Asn Trp Leu Ser Tyr195 200 205 ttc gcg gaa gcc ttc gcg gag cta gac acc cag caa ctg gtg cgggat 672 Phe Ala Glu Ala Phe Ala Glu Leu Asp Thr Gln Gln Leu Val Arg Asp210 215 220 gcc gag cgc aag ttt cga gga aga cgg gac gta gag gaa cct acggaa 720 Ala Glu Arg Lys Phe Arg Gly Arg Arg Asp Val Glu Glu Pro Thr Glu225 230 235 240 aca atg gcg aga tgt ttc atg agc act cta gcg agc gac gccgtt tcc 768 Thr Met Ala Arg Cys Phe Met Ser Thr Leu Ala Ser Asp Ala ValSer 245 250 255 tta gca gga acg ggt ctg tca gga ggc gcc atc acc ctc tgcagc cgg 816 Leu Ala Gly Thr Gly Leu Ser Gly Gly Ala Ile Thr Leu Cys SerArg 260 265 270 cgg gta acc gac cgc acc ggc ctg cgc cct aga gac cgc cacggc aga 864 Arg Val Thr Asp Arg Thr Gly Leu Arg Pro Arg Asp Arg His GlyArg 275 280 285 gcc atc acc gcg tcc gaa gcg cgc cgc att agg ccc cgt gccgtg cgg 912 Ala Ile Thr Ala Ser Glu Ala Arg Arg Ile Arg Pro Arg Ala ValArg 290 295 300 gcc ttc gta gac cgc ctg ccc cgc gtc acg cgg cgg cga cggaga ccc 960 Ala Phe Val Asp Arg Leu Pro Arg Val Thr Arg Arg Arg Arg ArgPro 305 310 315 320 ccc tcc ccc gcg ccc cct ccc gaa gaa ata gaa gaa gccgcc atg gaa 1008 Pro Ser Pro Ala Pro Pro Pro Glu Glu Ile Glu Glu Ala AlaMet Glu 325 330 335 gta gaa gaa cca gaa gag gag gaa gaa gag ctg tta gacgag gtg att 1056 Val Glu Glu Pro Glu Glu Glu Glu Glu Glu Leu Leu Asp GluVal Ile 340 345 350 cgc aca gcg ctc gaa gcc atc ggg gca ctg caa gac gagctc agc ggg 1104 Arg Thr Ala Leu Glu Ala Ile Gly Ala Leu Gln Asp Glu LeuSer Gly 355 360 365 gcc gcc cgg aga cac gaa ctc ttc agg ttt gcc aac gacttc tac cgc 1152 Ala Ala Arg Arg His Glu Leu Phe Arg Phe Ala Asn Asp PheTyr Arg 370 375 380 atg ctc ctg acc gcg cgc gac gcg gga ctc atg gga gagtcg ttc ctg 1200 Met Leu Leu Thr Ala Arg Asp Ala Gly Leu Met Gly Glu SerPhe Leu 385 390 395 400 cgc aag tgg gtg ctg tac ttc ttc tta gcc gaa catatc gcc tct aca 1248 Arg Lys Trp Val Leu Tyr Phe Phe Leu Ala Glu His IleAla Ser Thr 405 410 415 ctc tac tac ctg tac agc cac ttc atc gcc aac cgcgag ttc cgc cgg 1296 Leu Tyr Tyr Leu Tyr Ser His Phe Ile Ala Asn Arg GluPhe Arg Arg 420 425 430 tac gtc gac gtc ctg acc tta caa gta ctc gtc gtggga tgg gac gtc 1344 Tyr Val Asp Val Leu Thr Leu Gln Val Leu Val Val GlyTrp Asp Val 435 440 445 aac gcg cag cag gtt ttt aaa cgc ata tgg agc gagcaa tcc aac ccc 1392 Asn Ala Gln Gln Val Phe Lys Arg Ile Trp Ser Glu GlnSer Asn Pro 450 455 460 gcc acc ata ttc gaa acc ctg tgg gaa cgt ata ttacgc gat ttt ctt 1440 Ala Thr Ile Phe Glu Thr Leu Trp Glu Arg Ile Leu ArgAsp Phe Leu 465 470 475 480 atg atg gtc gaa cgg acg ggt caa ttc gaa ggcatg gac gat gcg gac 1488 Met Met Val Glu Arg Thr Gly Gln Phe Glu Gly MetAsp Asp Ala Asp 485 490 495 caa caa ctg ttt ctc tct gat att caa tac agagac cgc tcc ggt gac 1536 Gln Gln Leu Phe Leu Ser Asp Ile Gln Tyr Arg AspArg Ser Gly Asp 500 505 510 atc gaa gaa gtg ctg aag cag ctc aac ctc agcgaa gag ctg atc gat 1584 Ile Glu Glu Val Leu Lys Gln Leu Asn Leu Ser GluGlu Leu Ile Asp 515 520 525 agc atc gac atc agt ttc cgc atc aaa ttt aaaggc atc gta gcc atc 1632 Ser Ile Asp Ile Ser Phe Arg Ile Lys Phe Lys GlyIle Val Ala Ile 530 535 540 gct acc aac gag gag atc aaa gcc aac ctc agacgc gtg ctc cgc cac 1680 Ala Thr Asn Glu Glu Ile Lys Ala Asn Leu Arg ArgVal Leu Arg His 545 550 555 560 cgc cgc gaa gac atc gaa gcg gcg gcg cgacga ggt cag cct ctg taa 1728 Arg Arg Glu Asp Ile Glu Ala Ala Ala Arg ArgGly Gln Pro Leu 565 570 575 30 575 PRT CELO VIRUS Position10269..11996/Product E2b pTP 30 Met Gln Leu Arg Asp Leu Ala Pro Arg SerPro Asn Val Ala Ala Pro 1 5 10 15 Pro Tyr Asn Gly Leu Pro Pro Pro HisLeu Leu Leu Gly Tyr Gln Ala 20 25 30 Met His Arg Ala Leu Asn Asp Tyr LeuPhe Asp Asn Arg Val Phe Met 35 40 45 Gln Ile Gly Tyr Asp Ser Pro Pro GlnArg Pro Arg Arg Leu Phe Trp 50 55 60 Thr Cys Leu Thr Asp Cys Ser Tyr AlaVal Asn Val Gly Gln Tyr Met 65 70 75 80 Arg Phe Leu Asp Leu Asp Asn PheHis Gly Thr Phe Thr Gln Met His 85 90 95 Asn Ala Val Leu Met Asp Arg ValAla Ala Asp Met Gly Arg Ala His 100 105 110 Leu Arg Gly Arg Gly Ile AspVal Gly Arg His Gly Gln Val Leu Pro 115 120 125 Gln Leu Asp Ala Glu HisHis Ser Leu Leu Ser Gly Asn Gly Ala Gly 130 135 140 Gly Leu Gln Glu GlyVal Leu Met Arg Thr Ala Ser Ala Ala Asp Ala 145 150 155 160 Glu Leu LeuAla Ala Ile Arg Gln Leu Arg Val Ala Leu Cys His Tyr 165 170 175 Leu PheCys Tyr Ala Tyr Asp Leu Phe Gln Thr Glu Glu Arg Tyr Arg 180 185 190 PheLeu Pro Gly Ser Asp Val Phe Leu Glu Pro Asn Trp Leu Ser Tyr 195 200 205Phe Ala Glu Ala Phe Ala Glu Leu Asp Thr Gln Gln Leu Val Arg Asp 210 215220 Ala Glu Arg Lys Phe Arg Gly Arg Arg Asp Val Glu Glu Pro Thr Glu 225230 235 240 Thr Met Ala Arg Cys Phe Met Ser Thr Leu Ala Ser Asp Ala ValSer 245 250 255 Leu Ala Gly Thr Gly Leu Ser Gly Gly Ala Ile Thr Leu CysSer Arg 260 265 270 Arg Val Thr Asp Arg Thr Gly Leu Arg Pro Arg Asp ArgHis Gly Arg 275 280 285 Ala Ile Thr Ala Ser Glu Ala Arg Arg Ile Arg ProArg Ala Val Arg 290 295 300 Ala Phe Val Asp Arg Leu Pro Arg Val Thr ArgArg Arg Arg Arg Pro 305 310 315 320 Pro Ser Pro Ala Pro Pro Pro Glu GluIle Glu Glu Ala Ala Met Glu 325 330 335 Val Glu Glu Pro Glu Glu Glu GluGlu Glu Leu Leu Asp Glu Val Ile 340 345 350 Arg Thr Ala Leu Glu Ala IleGly Ala Leu Gln Asp Glu Leu Ser Gly 355 360 365 Ala Ala Arg Arg His GluLeu Phe Arg Phe Ala Asn Asp Phe Tyr Arg 370 375 380 Met Leu Leu Thr AlaArg Asp Ala Gly Leu Met Gly Glu Ser Phe Leu 385 390 395 400 Arg Lys TrpVal Leu Tyr Phe Phe Leu Ala Glu His Ile Ala Ser Thr 405 410 415 Leu TyrTyr Leu Tyr Ser His Phe Ile Ala Asn Arg Glu Phe Arg Arg 420 425 430 TyrVal Asp Val Leu Thr Leu Gln Val Leu Val Val Gly Trp Asp Val 435 440 445Asn Ala Gln Gln Val Phe Lys Arg Ile Trp Ser Glu Gln Ser Asn Pro 450 455460 Ala Thr Ile Phe Glu Thr Leu Trp Glu Arg Ile Leu Arg Asp Phe Leu 465470 475 480 Met Met Val Glu Arg Thr Gly Gln Phe Glu Gly Met Asp Asp AlaAsp 485 490 495 Gln Gln Leu Phe Leu Ser Asp Ile Gln Tyr Arg Asp Arg SerGly Asp 500 505 510 Ile Glu Glu Val Leu Lys Gln Leu Asn Leu Ser Glu GluLeu Ile Asp 515 520 525 Ser Ile Asp Ile Ser Phe Arg Ile Lys Phe Lys GlyIle Val Ala Ile 530 535 540 Ala Thr Asn Glu Glu Ile Lys Ala Asn Leu ArgArg Val Leu Arg His 545 550 555 560 Arg Arg Glu Asp Ile Glu Ala Ala AlaArg Arg Gly Gln Pro Leu 565 570 575 31 1320 DNA CELO VIRUS CDS(1)..(1320) 31 atg agc acc caa atc ccc gca cga cag gag acg tac gac ccgtcc caa 48 Met Ser Thr Gln Ile Pro Ala Arg Gln Glu Thr Tyr Asp Pro SerGln 1 5 10 15 tcg tcg ggc acg aag acc ccc tcg cac ccc tac gat ggg aaccct acg 96 Ser Ser Gly Thr Lys Thr Pro Ser His Pro Tyr Asp Gly Asn ProThr 20 25 30 cgt tcc tat ccg aag agg aat gcg ggc aag ttc acg acc tac tcttcg 144 Arg Ser Tyr Pro Lys Arg Asn Ala Gly Lys Phe Thr Thr Tyr Ser Ser35 40 45 cag atg ata gct ccc agg aag cgg aaa gcc tgg gag tat gag gaa gaa192 Gln Met Ile Ala Pro Arg Lys Arg Lys Ala Trp Glu Tyr Glu Glu Glu 5055 60 gag tac gaa gcc tcg cgg gac ttc tac cag cgc gtc acc agc tgg tac240 Glu Tyr Glu Ala Ser Arg Asp Phe Tyr Gln Arg Val Thr Ser Trp Tyr 6570 75 80 gac gga gct gtc gac cta gca ccg cag ctc ttc cgc gag caa cac ttc288 Asp Gly Ala Val Asp Leu Ala Pro Gln Leu Phe Arg Glu Gln His Phe 8590 95 ccc tcc tac gac gag ttc tac agc cta ggg ggc gtt aat gag aag ttt336 Pro Ser Tyr Asp Glu Phe Tyr Ser Leu Gly Gly Val Asn Glu Lys Phe 100105 110 ctc gaa gcc cac gaa gaa gtt aaa gcc cag gaa cag atg gac agt cgc384 Leu Glu Ala His Glu Glu Val Lys Ala Gln Glu Gln Met Asp Ser Arg 115120 125 tac ctc caa cac gga cag ctg ccg tcc atc aac atg ggc aag cag ccc432 Tyr Leu Gln His Gly Gln Leu Pro Ser Ile Asn Met Gly Lys Gln Pro 130135 140 atc atc ggg gtc atc tac gga ccc acc gga tcc ggc aag tcg cat ctg480 Ile Ile Gly Val Ile Tyr Gly Pro Thr Gly Ser Gly Lys Ser His Leu 145150 155 160 ctg cgg gcg ctc atc tcg tgc aac atg ttg gac ccg atc ccc gaaacg 528 Leu Arg Ala Leu Ile Ser Cys Asn Met Leu Asp Pro Ile Pro Glu Thr165 170 175 gtc atc ttc atc act ccg gaa aag aac atg att cca ccc atc gaacag 576 Val Ile Phe Ile Thr Pro Glu Lys Asn Met Ile Pro Pro Ile Glu Gln180 185 190 acg tcc tgg aac ctg cag ctg gtc gag gcc aat ttc gac tgc agggaa 624 Thr Ser Trp Asn Leu Gln Leu Val Glu Ala Asn Phe Asp Cys Arg Glu195 200 205 gac ggc acc atc gcc cct aag aca agc acg ttc cgt ccc gaa tttatg 672 Asp Gly Thr Ile Ala Pro Lys Thr Ser Thr Phe Arg Pro Glu Phe Met210 215 220 gag atg act tac gag gag gcc acc gca ccc gaa cat ctc aac atcgac 720 Glu Met Thr Tyr Glu Glu Ala Thr Ala Pro Glu His Leu Asn Ile Asp225 230 235 240 cat cca gac aac att tac gtg aaa gtc tcc aag cgg gga cccgtc gcc 768 His Pro Asp Asn Ile Tyr Val Lys Val Ser Lys Arg Gly Pro ValAla 245 250 255 att atc atg gac gag tgc atg gat aag ctc tgt tca ggc tccagc gtc 816 Ile Ile Met Asp Glu Cys Met Asp Lys Leu Cys Ser Gly Ser SerVal 260 265 270 tct gtc ctc ttt cac gcc ctt cct tct aag ctc ttt gct cgctct gcc 864 Ser Val Leu Phe His Ala Leu Pro Ser Lys Leu Phe Ala Arg SerAla 275 280 285 cac tgt aca gcc ttc tac att ttc gta gtc ttg cac aac atggca ccg 912 His Cys Thr Ala Phe Tyr Ile Phe Val Val Leu His Asn Met AlaPro 290 295 300 cgc acc gcg ata gga aac gtt ccc acc ctc aaa gtg aac gcgaaa atg 960 Arg Thr Ala Ile Gly Asn Val Pro Thr Leu Lys Val Asn Ala LysMet 305 310 315 320 cac atc cta tcc tgt cat att ccc caa ttc cag ttc gctagg ttc ctc 1008 His Ile Leu Ser Cys His Ile Pro Gln Phe Gln Phe Ala ArgPhe Leu 325 330 335 tat gcg ttc gca cac aac atc tcg aag gac ctc gtt gtcctt ctc aaa 1056 Tyr Ala Phe Ala His Asn Ile Ser Lys Asp Leu Val Val LeuLeu Lys 340 345 350 gct tac ttt tcc ttc ctg cag cag aac cag cgg ttc agctgg gtc atg 1104 Ala Tyr Phe Ser Phe Leu Gln Gln Asn Gln Arg Phe Ser TrpVal Met 355 360 365 tac act ccg gac cca gta tcc gag tcc ttt agg tgg tgcagt ata gat 1152 Tyr Thr Pro Asp Pro Val Ser Glu Ser Phe Arg Trp Cys SerIle Asp 370 375 380 cag cag tac tcg atc atc cct ctc aat gtt aac att caggag aga ttc 1200 Gln Gln Tyr Ser Ile Ile Pro Leu Asn Val Asn Ile Gln GluArg Phe 385 390 395 400 ctg aaa aca gcc aaa tct atc atc aaa ttt agc gaaaca cat aga aag 1248 Leu Lys Thr Ala Lys Ser Ile Ile Lys Phe Ser Glu ThrHis Arg Lys 405 410 415 cag tta gag aga aac ccc aaa cta acc gat ctc gaaaaa ctt tct ccc 1296 Gln Leu Glu Arg Asn Pro Lys Leu Thr Asp Leu Glu LysLeu Ser Pro 420 425 430 cca gga acg ttt cag gaa act taa 1320 Pro Gly ThrPhe Gln Glu Thr 435 440 32 439 PRT CELO VIRUS Position5366..6685/ProductIVa2 32 Met Ser Thr Gln Ile Pro Ala Arg Gln Glu ThrTyr Asp Pro Ser Gln 1 5 10 15 Ser Ser Gly Thr Lys Thr Pro Ser His ProTyr Asp Gly Asn Pro Thr 20 25 30 Arg Ser Tyr Pro Lys Arg Asn Ala Gly LysPhe Thr Thr Tyr Ser Ser 35 40 45 Gln Met Ile Ala Pro Arg Lys Arg Lys AlaTrp Glu Tyr Glu Glu Glu 50 55 60 Glu Tyr Glu Ala Ser Arg Asp Phe Tyr GlnArg Val Thr Ser Trp Tyr 65 70 75 80 Asp Gly Ala Val Asp Leu Ala Pro GlnLeu Phe Arg Glu Gln His Phe 85 90 95 Pro Ser Tyr Asp Glu Phe Tyr Ser LeuGly Gly Val Asn Glu Lys Phe 100 105 110 Leu Glu Ala His Glu Glu Val LysAla Gln Glu Gln Met Asp Ser Arg 115 120 125 Tyr Leu Gln His Gly Gln LeuPro Ser Ile Asn Met Gly Lys Gln Pro 130 135 140 Ile Ile Gly Val Ile TyrGly Pro Thr Gly Ser Gly Lys Ser His Leu 145 150 155 160 Leu Arg Ala LeuIle Ser Cys Asn Met Leu Asp Pro Ile Pro Glu Thr 165 170 175 Val Ile PheIle Thr Pro Glu Lys Asn Met Ile Pro Pro Ile Glu Gln 180 185 190 Thr SerTrp Asn Leu Gln Leu Val Glu Ala Asn Phe Asp Cys Arg Glu 195 200 205 AspGly Thr Ile Ala Pro Lys Thr Ser Thr Phe Arg Pro Glu Phe Met 210 215 220Glu Met Thr Tyr Glu Glu Ala Thr Ala Pro Glu His Leu Asn Ile Asp 225 230235 240 His Pro Asp Asn Ile Tyr Val Lys Val Ser Lys Arg Gly Pro Val Ala245 250 255 Ile Ile Met Asp Glu Cys Met Asp Lys Leu Cys Ser Gly Ser SerVal 260 265 270 Ser Val Leu Phe His Ala Leu Pro Ser Lys Leu Phe Ala ArgSer Ala 275 280 285 His Cys Thr Ala Phe Tyr Ile Phe Val Val Leu His AsnMet Ala Pro 290 295 300 Arg Thr Ala Ile Gly Asn Val Pro Thr Leu Lys ValAsn Ala Lys Met 305 310 315 320 His Ile Leu Ser Cys His Ile Pro Gln PheGln Phe Ala Arg Phe Leu 325 330 335 Tyr Ala Phe Ala His Asn Ile Ser LysAsp Leu Val Val Leu Leu Lys 340 345 350 Ala Tyr Phe Ser Phe Leu Gln GlnAsn Gln Arg Phe Ser Trp Val Met 355 360 365 Tyr Thr Pro Asp Pro Val SerGlu Ser Phe Arg Trp Cys Ser Ile Asp 370 375 380 Gln Gln Tyr Ser Ile IlePro Leu Asn Val Asn Ile Gln Glu Arg Phe 385 390 395 400 Leu Lys Thr AlaLys Ser Ile Ile Lys Phe Ser Glu Thr His Arg Lys 405 410 415 Gln Leu GluArg Asn Pro Lys Leu Thr Asp Leu Glu Lys Leu Ser Pro 420 425 430 Pro GlyThr Phe Gln Glu Thr 435 33 633 DNA CELO VIRUS CDS (1)..(633) 33 atg ctagaa gcc gaa ggt tac aat gct ccg gta gcc atc tac gcc att 48 Met Leu GluAla Glu Gly Tyr Asn Ala Pro Val Ala Ile Tyr Ala Ile 1 5 10 15 tat ctgtgg atg tct gcc atg agc att agt cgc ctg tgc cat tat act 96 Tyr Leu TrpMet Ser Ala Met Ser Ile Ser Arg Leu Cys His Tyr Thr 20 25 30 aac acg ctctat gtc gta gga gaa cct tcc tct gcc gca gat ata ttc 144 Asn Thr Leu TyrVal Val Gly Glu Pro Ser Ser Ala Ala Asp Ile Phe 35 40 45 act gca tcc atcctc aga tta ttc caa ttt gtc ctc act gcc aac att 192 Thr Ala Ser Ile LeuArg Leu Phe Gln Phe Val Leu Thr Ala Asn Ile 50 55 60 aac gcg ttc gac tttggc cag tac gcc aga cag caa gat tta gtc aag 240 Asn Ala Phe Asp Phe GlyGln Tyr Ala Arg Gln Gln Asp Leu Val Lys 65 70 75 80 atg ctt tat ttc ccctgc aca gct cat tgt aac acg ttc aaa gat ccc 288 Met Leu Tyr Phe Pro CysThr Ala His Cys Asn Thr Phe Lys Asp Pro 85 90 95 gtt gct aac cag ctg ctgaaa ggc agg tca ttc acc aca atg acc cgc 336 Val Ala Asn Gln Leu Leu LysGly Arg Ser Phe Thr Thr Met Thr Arg 100 105 110 gac ggt ctc gtg gac atcagt gag aaa aaa tgc ctc gtc cgc tta tat 384 Asp Gly Leu Val Asp Ile SerGlu Lys Lys Cys Leu Val Arg Leu Tyr 115 120 125 cag ctc ccc cat ccc gaacat ctg ccc act gct ccc gac gaa cat atc 432 Gln Leu Pro His Pro Glu HisLeu Pro Thr Ala Pro Asp Glu His Ile 130 135 140 att att agg ttc tac gaaccc gcc aac ggc tgc ggg ttc ttt ctg gga 480 Ile Ile Arg Phe Tyr Glu ProAla Asn Gly Cys Gly Phe Phe Leu Gly 145 150 155 160 gag ctc tcc cgc tacatt cat cgc ata cac caa tta cag gca gat aat 528 Glu Leu Ser Arg Tyr IleHis Arg Ile His Gln Leu Gln Ala Asp Asn 165 170 175 gac aac gac gcc ttgcgc gct ctc cta tgc gag aac aaa gga atg ctc 576 Asp Asn Asp Ala Leu ArgAla Leu Leu Cys Glu Asn Lys Gly Met Leu 180 185 190 tgt tcc cgc tcg tggacc tcc cca tgc aat gct tgt cac tca tca cat 624 Cys Ser Arg Ser Trp ThrSer Pro Cys Asn Ala Cys His Ser Ser His 195 200 205 gac ata taa 633 AspIle 210 34 210 PRT CELO VIRUS Position 4462..5094/note=ORF12 34 Met LeuGlu Ala Glu Gly Tyr Asn Ala Pro Val Ala Ile Tyr Ala Ile 1 5 10 15 TyrLeu Trp Met Ser Ala Met Ser Ile Ser Arg Leu Cys His Tyr Thr 20 25 30 AsnThr Leu Tyr Val Val Gly Glu Pro Ser Ser Ala Ala Asp Ile Phe 35 40 45 ThrAla Ser Ile Leu Arg Leu Phe Gln Phe Val Leu Thr Ala Asn Ile 50 55 60 AsnAla Phe Asp Phe Gly Gln Tyr Ala Arg Gln Gln Asp Leu Val Lys 65 70 75 80Met Leu Tyr Phe Pro Cys Thr Ala His Cys Asn Thr Phe Lys Asp Pro 85 90 95Val Ala Asn Gln Leu Leu Lys Gly Arg Ser Phe Thr Thr Met Thr Arg 100 105110 Asp Gly Leu Val Asp Ile Ser Glu Lys Lys Cys Leu Val Arg Leu Tyr 115120 125 Gln Leu Pro His Pro Glu His Leu Pro Thr Ala Pro Asp Glu His Ile130 135 140 Ile Ile Arg Phe Tyr Glu Pro Ala Asn Gly Cys Gly Phe Phe LeuGly 145 150 155 160 Glu Leu Ser Arg Tyr Ile His Arg Ile His Gln Leu GlnAla Asp Asn 165 170 175 Asp Asn Asp Ala Leu Arg Ala Leu Leu Cys Glu AsnLys Gly Met Leu 180 185 190 Cys Ser Arg Ser Trp Thr Ser Pro Cys Asn AlaCys His Ser Ser His 195 200 205 Asp Ile 210 35 1020 DNA CELO VIRUS CDS(1)..(1020) 35 atg aca acg acg cct tgc gcg ctc tcc tat gcg aga aca aaggaa tgc 48 Met Thr Thr Thr Pro Cys Ala Leu Ser Tyr Ala Arg Thr Lys GluCys 1 5 10 15 tct gtt ccc gct cgt gga cct ccc cat gca atg ctt gtc actcat cac 96 Ser Val Pro Ala Arg Gly Pro Pro His Ala Met Leu Val Thr HisHis 20 25 30 atg aca tat aat tct ctc cca cag tgc acc aag agg cga cgc gagtct 144 Met Thr Tyr Asn Ser Leu Pro Gln Cys Thr Lys Arg Arg Arg Glu Ser35 40 45 cag tcg tct tta agt agc gaa gag gag caa ata gca tcc tgc att cca192 Gln Ser Ser Leu Ser Ser Glu Glu Glu Gln Ile Ala Ser Cys Ile Pro 5055 60 gac acc cct tca ccc tgc tta ttt ccg tcc acg tcc ccc atg gat cag240 Asp Thr Pro Ser Pro Cys Leu Phe Pro Ser Thr Ser Pro Met Asp Gln 6570 75 80 ttg gtt gaa cgg ttg ttt gtc gaa ggt gta gca cac gaa gtc cag tgg288 Leu Val Glu Arg Leu Phe Val Glu Gly Val Ala His Glu Val Gln Trp 8590 95 aac ttc ccg tcc aag aac ctc ata ccc acc tac gaa cga gag cgt gta336 Asn Phe Pro Ser Lys Asn Leu Ile Pro Thr Tyr Glu Arg Glu Arg Val 100105 110 ctc gaa gcc ctc aag gaa cgg ttc gga ccc gga cag agc ctc att aac384 Leu Glu Ala Leu Lys Glu Arg Phe Gly Pro Gly Gln Ser Leu Ile Asn 115120 125 cag tta ccc tcc gaa gag ccc gac acc ctc aag gct gcg ttc tac aac432 Gln Leu Pro Ser Glu Glu Pro Asp Thr Leu Lys Ala Ala Phe Tyr Asn 130135 140 gtc tgc gac aac tgg ttc cat cag atg atg gaa gcc gaa ggc tac gag480 Val Cys Asp Asn Trp Phe His Gln Met Met Glu Ala Glu Gly Tyr Glu 145150 155 160 gga aaa gtg gca gct aac gcc atc ctc cga tgg ctc cga gga gaacta 528 Gly Lys Val Ala Ala Asn Ala Ile Leu Arg Trp Leu Arg Gly Glu Leu165 170 175 aac acc ctc gtg ctc tgc gga gga aga ctt tcc aac gcc aag agtctc 576 Asn Thr Leu Val Leu Cys Gly Gly Arg Leu Ser Asn Ala Lys Ser Leu180 185 190 ttt aat gcc tta tgc gcg tgt ttc ccg ctc gcg atc tcc gac agccga 624 Phe Asn Ala Leu Cys Ala Cys Phe Pro Leu Ala Ile Ser Asp Ser Arg195 200 205 atc aac tcc ata cta tca ctg ggc gaa atc gca ccc cac gcc tctcta 672 Ile Asn Ser Ile Leu Ser Leu Gly Glu Ile Ala Pro His Ala Ser Leu210 215 220 tac tgt ctg ccc ttc gta gac gag aag ccg gac ccg ttg atg ctgcac 720 Tyr Cys Leu Pro Phe Val Asp Glu Lys Pro Asp Pro Leu Met Leu His225 230 235 240 ttt atg gaa ggc aat gct gcc acc tgc agg ctg aat aag aaaacg ttc 768 Phe Met Glu Gly Asn Ala Ala Thr Cys Arg Leu Asn Lys Lys ThrPhe 245 250 255 cac atc ccc tcg acc ccc atg cta atc cac tgc gcg gac ctctcg ctc 816 His Ile Pro Ser Thr Pro Met Leu Ile His Cys Ala Asp Leu SerLeu 260 265 270 gcc aac gag ttc acg gcg cgg aac acg gtc gtc ttc ttc ctcaca gga 864 Ala Asn Glu Phe Thr Ala Arg Asn Thr Val Val Phe Phe Leu ThrGly 275 280 285 gac cac acc aag acc cct cca tgc tac cac ccg cgc aaa gagcta cgc 912 Asp His Thr Lys Thr Pro Pro Cys Tyr His Pro Arg Lys Glu LeuArg 290 295 300 gac ttt gtt gct aat gct gcc gct tgt gct tgc tta atg acactg cat 960 Asp Phe Val Ala Asn Ala Ala Ala Cys Ala Cys Leu Met Thr LeuHis 305 310 315 320 tgc aaa cgc gat aat aaa ctc tgt aac ccc tgt ata cgtacc cct ctt 1008 Cys Lys Arg Asp Asn Lys Leu Cys Asn Pro Cys Ile Arg ThrPro Leu 325 330 335 caa aat cag taa 1020 Gln Asn Gln 340 36 339 PRT CELOVIRUS Position 3549..4568/note=ORF13 36 Met Thr Thr Thr Pro Cys Ala LeuSer Tyr Ala Arg Thr Lys Glu Cys 1 5 10 15 Ser Val Pro Ala Arg Gly ProPro His Ala Met Leu Val Thr His His 20 25 30 Met Thr Tyr Asn Ser Leu ProGln Cys Thr Lys Arg Arg Arg Glu Ser 35 40 45 Gln Ser Ser Leu Ser Ser GluGlu Glu Gln Ile Ala Ser Cys Ile Pro 50 55 60 Asp Thr Pro Ser Pro Cys LeuPhe Pro Ser Thr Ser Pro Met Asp Gln 65 70 75 80 Leu Val Glu Arg Leu PheVal Glu Gly Val Ala His Glu Val Gln Trp 85 90 95 Asn Phe Pro Ser Lys AsnLeu Ile Pro Thr Tyr Glu Arg Glu Arg Val 100 105 110 Leu Glu Ala Leu LysGlu Arg Phe Gly Pro Gly Gln Ser Leu Ile Asn 115 120 125 Gln Leu Pro SerGlu Glu Pro Asp Thr Leu Lys Ala Ala Phe Tyr Asn 130 135 140 Val Cys AspAsn Trp Phe His Gln Met Met Glu Ala Glu Gly Tyr Glu 145 150 155 160 GlyLys Val Ala Ala Asn Ala Ile Leu Arg Trp Leu Arg Gly Glu Leu 165 170 175Asn Thr Leu Val Leu Cys Gly Gly Arg Leu Ser Asn Ala Lys Ser Leu 180 185190 Phe Asn Ala Leu Cys Ala Cys Phe Pro Leu Ala Ile Ser Asp Ser Arg 195200 205 Ile Asn Ser Ile Leu Ser Leu Gly Glu Ile Ala Pro His Ala Ser Leu210 215 220 Tyr Cys Leu Pro Phe Val Asp Glu Lys Pro Asp Pro Leu Met LeuHis 225 230 235 240 Phe Met Glu Gly Asn Ala Ala Thr Cys Arg Leu Asn LysLys Thr Phe 245 250 255 His Ile Pro Ser Thr Pro Met Leu Ile His Cys AlaAsp Leu Ser Leu 260 265 270 Ala Asn Glu Phe Thr Ala Arg Asn Thr Val ValPhe Phe Leu Thr Gly 275 280 285 Asp His Thr Lys Thr Pro Pro Cys Tyr HisPro Arg Lys Glu Leu Arg 290 295 300 Asp Phe Val Ala Asn Ala Ala Ala CysAla Cys Leu Met Thr Leu His 305 310 315 320 Cys Lys Arg Asp Asn Lys LeuCys Asn Pro Cys Ile Arg Thr Pro Leu 325 330 335 Gln Asn Gln 37 483 DNACELO VIRUS CDS (1)..(483) 37 atg tac ccc ttc aag cac tcg ccc cac tgc attacg gac gaa gag tgt 48 Met Tyr Pro Phe Lys His Ser Pro His Cys Ile ThrAsp Glu Glu Cys 1 5 10 15 gac ctc cag ctc agg tca ttc tgc agc tgg ataaga gtt att gag atg 96 Asp Leu Gln Leu Arg Ser Phe Cys Ser Trp Ile ArgVal Ile Glu Met 20 25 30 cga tgt acc gac tgg act atc cag tac atc tgc agctgc gag aca ccc 144 Arg Cys Thr Asp Trp Thr Ile Gln Tyr Ile Cys Ser CysGlu Thr Pro 35 40 45 cgt tcc ctc ttt tgt tta tcc ctc atc cga gtg ctt acagct cac tgg 192 Arg Ser Leu Phe Cys Leu Ser Leu Ile Arg Val Leu Thr AlaHis Trp 50 55 60 gcc aaa acg gtc gtc aat ttc gtt gct caa cac gac cac cagccc caa 240 Ala Lys Thr Val Val Asn Phe Val Ala Gln His Asp His Gln ProGln 65 70 75 80 ctc cct ctt aat ctc atc tta tac aca tat gct act cac tgcagg tta 288 Leu Pro Leu Asn Leu Ile Leu Tyr Thr Tyr Ala Thr His Cys ArgLeu 85 90 95 tgc aac ttg aac cct gcc ctc gaa caa ata tat aca gca gta accgtt 336 Cys Asn Leu Asn Pro Ala Leu Glu Gln Ile Tyr Thr Ala Val Thr Val100 105 110 gcg cgg cgc caa ggc gcc tac acg cga ctg gaa gga caa aca ctctat 384 Ala Arg Arg Gln Gly Ala Tyr Thr Arg Leu Glu Gly Gln Thr Leu Tyr115 120 125 gtc tgt ctt cca agg gac atc gta aac tat ccc tgc ata gct tgcttt 432 Val Cys Leu Pro Arg Asp Ile Val Asn Tyr Pro Cys Ile Ala Cys Phe130 135 140 tac cac ctg ctt ctg cgg ctc cca gtc gca att aac ttc cac gtgata 480 Tyr His Leu Leu Leu Arg Leu Pro Val Ala Ile Asn Phe His Val Ile145 150 155 160 tga 483 38 160 PRT CELO VIRUS Position2892..3374/note=ORF14 38 Met Tyr Pro Phe Lys His Ser Pro His Cys Ile ThrAsp Glu Glu Cys 1 5 10 15 Asp Leu Gln Leu Arg Ser Phe Cys Ser Trp IleArg Val Ile Glu Met 20 25 30 Arg Cys Thr Asp Trp Thr Ile Gln Tyr Ile CysSer Cys Glu Thr Pro 35 40 45 Arg Ser Leu Phe Cys Leu Ser Leu Ile Arg ValLeu Thr Ala His Trp 50 55 60 Ala Lys Thr Val Val Asn Phe Val Ala Gln HisAsp His Gln Pro Gln 65 70 75 80 Leu Pro Leu Asn Leu Ile Leu Tyr Thr TyrAla Thr His Cys Arg Leu 85 90 95 Cys Asn Leu Asn Pro Ala Leu Glu Gln IleTyr Thr Ala Val Thr Val 100 105 110 Ala Arg Arg Gln Gly Ala Tyr Thr ArgLeu Glu Gly Gln Thr Leu Tyr 115 120 125 Val Cys Leu Pro Arg Asp Ile ValAsn Tyr Pro Cys Ile Ala Cys Phe 130 135 140 Tyr His Leu Leu Leu Arg LeuPro Val Ala Ile Asn Phe His Val Ile 145 150 155 160 39 324 DNA CELOVIRUS CDS (1)..(324) 39 atg gtc gcg agc tgc cac acg ctc aca atc ata cctaaa gaa gca cgc 48 Met Val Ala Ser Cys His Thr Leu Thr Ile Ile Pro LysGlu Ala Arg 1 5 10 15 agt aac tgt tac aga gcg tac agc agg gcc tct tgctgg tgc tgc ctt 96 Ser Asn Cys Tyr Arg Ala Tyr Ser Arg Ala Ser Cys TrpCys Cys Leu 20 25 30 cgc aca gac aat gtc cgt atg tgt cgt cgt ccc cct caaaat ctg ctt 144 Arg Thr Asp Asn Val Arg Met Cys Arg Arg Pro Pro Gln AsnLeu Leu 35 40 45 gca agc gta cag cga agt cga ctt cgt cgc aag ggt cct atcaac ggg 192 Ala Ser Val Gln Arg Ser Arg Leu Arg Arg Lys Gly Pro Ile AsnGly 50 55 60 aac cag ggg tca gcc att cca aca cag agc gct gat tgc ggt ctacag 240 Asn Gln Gly Ser Ala Ile Pro Thr Gln Ser Ala Asp Cys Gly Leu Gln65 70 75 80 cac cca tac ctg tgg acc cga aac ccg acg ccc cgc ggt ctg tctcgc 288 His Pro Tyr Leu Trp Thr Arg Asn Pro Thr Pro Arg Gly Leu Ser Arg85 90 95 cta gct gcg tca gtt ccg aca gct ccg gaa cca taa 324 Leu Ala AlaSer Val Pro Thr Ala Pro Glu Pro 100 105 40 107 PRT CELO VIRUSPosition1191..1514/note=ORF15 40 Met Val Ala Ser Cys His Thr Leu Thr IleIle Pro Lys Glu Ala Arg 1 5 10 15 Ser Asn Cys Tyr Arg Ala Tyr Ser ArgAla Ser Cys Trp Cys Cys Leu 20 25 30 Arg Thr Asp Asn Val Arg Met Cys ArgArg Pro Pro Gln Asn Leu Leu 35 40 45 Ala Ser Val Gln Arg Ser Arg Leu ArgArg Lys Gly Pro Ile Asn Gly 50 55 60 Asn Gln Gly Ser Ala Ile Pro Thr GlnSer Ala Asp Cys Gly Leu Gln 65 70 75 80 His Pro Tyr Leu Trp Thr Arg AsnPro Thr Pro Arg Gly Leu Ser Arg 85 90 95 Leu Ala Ala Ser Val Pro Thr AlaPro Glu Pro 100 105 41 417 DNA CELO VIRUS CDS (1)..(417) 41 atg tat tacttc cac ctc cgc gtg acc ttg atg gag cct aac ttg gcc 48 Met Tyr Tyr PheHis Leu Arg Val Thr Leu Met Glu Pro Asn Leu Ala 1 5 10 15 gta ttc catgat ctg aaa ttg acg gtg ata aat gcc tgg gaa agt tta 96 Val Phe His AspLeu Lys Leu Thr Val Ile Asn Ala Trp Glu Ser Leu 20 25 30 act gtt gag atgctg tcc cac tat agt gta gat tac ctg ttc cga ttg 144 Thr Val Glu Met LeuSer His Tyr Ser Val Asp Tyr Leu Phe Arg Leu 35 40 45 gag gag ttt gcg ggggta tat tca gct tct att ttt ttg ccc acg cat 192 Glu Glu Phe Ala Gly ValTyr Ser Ala Ser Ile Phe Leu Pro Thr His 50 55 60 aag gtt gat tgg act ttcttg aaa agg gcg gtg gct tta ctg cgc gaa 240 Lys Val Asp Trp Thr Phe LeuLys Arg Ala Val Ala Leu Leu Arg Glu 65 70 75 80 tgt att tgg agg aga tttgaa tgt aca cag gtt ccg cga ggg gtg gct 288 Cys Ile Trp Arg Arg Phe GluCys Thr Gln Val Pro Arg Gly Val Ala 85 90 95 tct att tac gcg gtg cgc aatacg tgg acc ccc tcc gcc aat agg gtg 336 Ser Ile Tyr Ala Val Arg Asn ThrTrp Thr Pro Ser Ala Asn Arg Val 100 105 110 gcc cgt cac ttt gta aaa cgcggg gca ttg gtt ggc atg cag ccc tgt 384 Ala Arg His Phe Val Lys Arg GlyAla Leu Val Gly Met Gln Pro Cys 115 120 125 tta cac gaa tgt acc tat gagcgg gat gcc tgt 417 Leu His Glu Cys Thr Tyr Glu Arg Asp Ala Cys 130 13542 139 PRT CELO VIRUS Position39286..39705/note=ORF16 42 Met Tyr Tyr PheHis Leu Arg Val Thr Leu Met Glu Pro Asn Leu Ala 1 5 10 15 Val Phe HisAsp Leu Lys Leu Thr Val Ile Asn Ala Trp Glu Ser Leu 20 25 30 Thr Val GluMet Leu Ser His Tyr Ser Val Asp Tyr Leu Phe Arg Leu 35 40 45 Glu Glu PheAla Gly Val Tyr Ser Ala Ser Ile Phe Leu Pro Thr His 50 55 60 Lys Val AspTrp Thr Phe Leu Lys Arg Ala Val Ala Leu Leu Arg Glu 65 70 75 80 Cys IleTrp Arg Arg Phe Glu Cys Thr Gln Val Pro Arg Gly Val Ala 85 90 95 Ser IleTyr Ala Val Arg Asn Thr Trp Thr Pro Ser Ala Asn Arg Val 100 105 110 AlaArg His Phe Val Lys Arg Gly Ala Leu Val Gly Met Gln Pro Cys 115 120 125Leu His Glu Cys Thr Tyr Glu Arg Asp Ala Cys 130 135 43 540 DNA CELOVIRUS CDS (1)..(540) 43 atg cct ttg tat ttg tgc ttt ggg gcc gcc gcc ccggtt tcg att ttg 48 Met Pro Leu Tyr Leu Cys Phe Gly Ala Ala Ala Pro ValSer Ile Leu 1 5 10 15 tgg cgg gaa gaa ctc ttc tgg gga ttc gtg gct gcggtc aag agg agg 96 Trp Arg Glu Glu Leu Phe Trp Gly Phe Val Ala Ala ValLys Arg Arg 20 25 30 tgg cac act gta tat gca cgg acc aat gtg gac att cagtat ccg atg 144 Trp His Thr Val Tyr Ala Arg Thr Asn Val Asp Ile Gln TyrPro Met 35 40 45 gcg tat tgt gtc ggt atc caa tcc ctg tct cca tgc aaa tgtcat gtg 192 Ala Tyr Cys Val Gly Ile Gln Ser Leu Ser Pro Cys Lys Cys HisVal 50 55 60 acc gtg gtg gtg tgt ctg acc ttt ctg gat ctg cgc atg tcc gctatt 240 Thr Val Val Val Cys Leu Thr Phe Leu Asp Leu Arg Met Ser Ala Ile65 70 75 80 aat gaa gcc acg aaa ata atg cgc gcg ttt ttc aaa acc ttt ttctac 288 Asn Glu Ala Thr Lys Ile Met Arg Ala Phe Phe Lys Thr Phe Phe Tyr85 90 95 cac cac ggg aaa gtc ccg cgt ggg cgg tgg ttt aaa ttg tac aga aat336 His His Gly Lys Val Pro Arg Gly Arg Trp Phe Lys Leu Tyr Arg Asn 100105 110 gat tgg tgt aag gat cct aat tta aca gtg ggt aat tac att gtg gca384 Asp Trp Cys Lys Asp Pro Asn Leu Thr Val Gly Asn Tyr Ile Val Ala 115120 125 tcg ggg gcg tta cct ttg atg ctg ggg tgg gcg cgg tct acg ggg ttg432 Ser Gly Ala Leu Pro Leu Met Leu Gly Trp Ala Arg Ser Thr Gly Leu 130135 140 cgg ttc agc aca ttt aca tat tca gat gag gct ctg tgg agt cat aga480 Arg Phe Ser Thr Phe Thr Tyr Ser Asp Glu Ala Leu Trp Ser His Arg 145150 155 160 cgg aga gat agg agg ctt gcc cgt cgg cgg gaa aag ctt gaa aataaa 528 Arg Arg Asp Arg Arg Leu Ala Arg Arg Arg Glu Lys Leu Glu Asn Lys165 170 175 gta tca ggt tga 540 Val Ser Gly 180 44 179 PRT CELO VIRUSPosition38717..39256/note=ORF17 44 Met Pro Leu Tyr Leu Cys Phe Gly AlaAla Ala Pro Val Ser Ile Leu 1 5 10 15 Trp Arg Glu Glu Leu Phe Trp GlyPhe Val Ala Ala Val Lys Arg Arg 20 25 30 Trp His Thr Val Tyr Ala Arg ThrAsn Val Asp Ile Gln Tyr Pro Met 35 40 45 Ala Tyr Cys Val Gly Ile Gln SerLeu Ser Pro Cys Lys Cys His Val 50 55 60 Thr Val Val Val Cys Leu Thr PheLeu Asp Leu Arg Met Ser Ala Ile 65 70 75 80 Asn Glu Ala Thr Lys Ile MetArg Ala Phe Phe Lys Thr Phe Phe Tyr 85 90 95 His His Gly Lys Val Pro ArgGly Arg Trp Phe Lys Leu Tyr Arg Asn 100 105 110 Asp Trp Cys Lys Asp ProAsn Leu Thr Val Gly Asn Tyr Ile Val Ala 115 120 125 Ser Gly Ala Leu ProLeu Met Leu Gly Trp Ala Arg Ser Thr Gly Leu 130 135 140 Arg Phe Ser ThrPhe Thr Tyr Ser Asp Glu Ala Leu Trp Ser His Arg 145 150 155 160 Arg ArgAsp Arg Arg Leu Ala Arg Arg Arg Glu Lys Leu Glu Asn Lys 165 170 175 ValSer Gly 45 609 DNA CELO VIRUS CDS (1)..(609) 45 atg tct gcc cta tct tcgtgc ttt aat ggg tcg gat tcc aga tgg gat 48 Met Ser Ala Leu Ser Ser CysPhe Asn Gly Ser Asp Ser Arg Trp Asp 1 5 10 15 ccg cca tat cct aag gctgac gtc agg cgc ttg atg ggc acc tat tcg 96 Pro Pro Tyr Pro Lys Ala AspVal Arg Arg Leu Met Gly Thr Tyr Ser 20 25 30 ccg gat ttt cct tcg tgg cccaag tta att gta tgg tgg aat gag act 144 Pro Asp Phe Pro Ser Trp Pro LysLeu Ile Val Trp Trp Asn Glu Thr 35 40 45 ttt ttg act ttt tcg gac ggc ccctgg gtt gtc agt caa atg cgg cgg 192 Phe Leu Thr Phe Ser Asp Gly Pro TrpVal Val Ser Gln Met Arg Arg 50 55 60 ctc ggg gta ttg gat ggt aaa gat agcggg gag ctc att att ctg gtt 240 Leu Gly Val Leu Asp Gly Lys Asp Ser GlyGlu Leu Ile Ile Leu Val 65 70 75 80 cag gac atg tat ccc gat gtg tgt ccgctt att aat agg gcg cgc tat 288 Gln Asp Met Tyr Pro Asp Val Cys Pro LeuIle Asn Arg Ala Arg Tyr 85 90 95 gac ggc aca tat aaa tgg acc agt gaa atgatg aga aag att ttg cgt 336 Asp Gly Thr Tyr Lys Trp Thr Ser Glu Met MetArg Lys Ile Leu Arg 100 105 110 atg cat acc att atg acg cca gag tcc ccggtc att ctg ttg gac tgg 384 Met His Thr Ile Met Thr Pro Glu Ser Pro ValIle Leu Leu Asp Trp 115 120 125 acc aat cag ctg aga gat att tgt aag aaggta gac gcc ctt ttg tgg 432 Thr Asn Gln Leu Arg Asp Ile Cys Lys Lys ValAsp Ala Leu Leu Trp 130 135 140 ggg cag gat gtg agg ggg ccg gcc tat tacgca gtc agg acc act gct 480 Gly Gln Asp Val Arg Gly Pro Ala Tyr Tyr AlaVal Arg Thr Thr Ala 145 150 155 160 cat ttt ttt acg gag ttc aag gac catcga att cat tgc ata ggg atg 528 His Phe Phe Thr Glu Phe Lys Asp His ArgIle His Cys Ile Gly Met 165 170 175 tcg cta ggg ggc act gta tgc gcg gctttg tcc cgc caa ctt cta gtc 576 Ser Leu Gly Gly Thr Val Cys Ala Ala LeuSer Arg Gln Leu Leu Val 180 185 190 cgg aca gag ggt caa aaa agg ttg gccgca tag 609 Arg Thr Glu Gly Gln Lys Arg Leu Ala Ala 195 200 46 202 PRTCELO VIRUS Position35536..36144/note=ORF18 46 Met Ser Ala Leu Ser SerCys Phe Asn Gly Ser Asp Ser Arg Trp Asp 1 5 10 15 Pro Pro Tyr Pro LysAla Asp Val Arg Arg Leu Met Gly Thr Tyr Ser 20 25 30 Pro Asp Phe Pro SerTrp Pro Lys Leu Ile Val Trp Trp Asn Glu Thr 35 40 45 Phe Leu Thr Phe SerAsp Gly Pro Trp Val Val Ser Gln Met Arg Arg 50 55 60 Leu Gly Val Leu AspGly Lys Asp Ser Gly Glu Leu Ile Ile Leu Val 65 70 75 80 Gln Asp Met TyrPro Asp Val Cys Pro Leu Ile Asn Arg Ala Arg Tyr 85 90 95 Asp Gly Thr TyrLys Trp Thr Ser Glu Met Met Arg Lys Ile Leu Arg 100 105 110 Met His ThrIle Met Thr Pro Glu Ser Pro Val Ile Leu Leu Asp Trp 115 120 125 Thr AsnGln Leu Arg Asp Ile Cys Lys Lys Val Asp Ala Leu Leu Trp 130 135 140 GlyGln Asp Val Arg Gly Pro Ala Tyr Tyr Ala Val Arg Thr Thr Ala 145 150 155160 His Phe Phe Thr Glu Phe Lys Asp His Arg Ile His Cys Ile Gly Met 165170 175 Ser Leu Gly Gly Thr Val Cys Ala Ala Leu Ser Arg Gln Leu Leu Val180 185 190 Arg Thr Glu Gly Gln Lys Arg Leu Ala Ala 195 200 47 1362 DNACELO VIRUS CDS (1)..(1362) 47 atg cgc ggc ttt gtc ccg cca act tct agtccg gac aga ggg tca aaa 48 Met Arg Gly Phe Val Pro Pro Thr Ser Ser ProAsp Arg Gly Ser Lys 1 5 10 15 aag gtt ggc cgc ata gtg gcg cta gat ccccca ttg gaa agt ttc cag 96 Lys Val Gly Arg Ile Val Ala Leu Asp Pro ProLeu Glu Ser Phe Gln 20 25 30 ggt tat agg atg gac tta cac aca aaa ggg ttaaac ctt ttg ctg tct 144 Gly Tyr Arg Met Asp Leu His Thr Lys Gly Leu AsnLeu Leu Leu Ser 35 40 45 tcc ggt ggt cat tgg tca gcc aat agg gat gcg gatagt gtt atc tct 192 Ser Gly Gly His Trp Ser Ala Asn Arg Asp Ala Asp SerVal Ile Ser 50 55 60 agg gat gac gcg gat tac gta gtg gtg att gcg tct agtatt ggt tcg 240 Arg Asp Asp Ala Asp Tyr Val Val Val Ile Ala Ser Ser IleGly Ser 65 70 75 80 tac ggt ttt gat cga cca ata gga gac gag tat ata cggagc gat ctg 288 Tyr Gly Phe Asp Arg Pro Ile Gly Asp Glu Tyr Ile Arg SerAsp Leu 85 90 95 act ggt caa aaa cat gag gct tgc gag tca cgt gct tgg tggaaa ggt 336 Thr Gly Gln Lys His Glu Ala Cys Glu Ser Arg Ala Trp Trp LysGly 100 105 110 caa atc tgt gca tgg tct tat tct ggg agg cgc cat tgt gaagat gta 384 Gln Ile Cys Ala Trp Ser Tyr Ser Gly Arg Arg His Cys Glu AspVal 115 120 125 cat att ccc ttt gat ttc ctc cga tcg gat gga ctg tgt tatcac att 432 His Ile Pro Phe Asp Phe Leu Arg Ser Asp Gly Leu Cys Tyr HisIle 130 135 140 atg gcg cct ttg acc ttt atg aag gcc ctg gat act cac caggct gac 480 Met Ala Pro Leu Thr Phe Met Lys Ala Leu Asp Thr His Gln AlaAsp 145 150 155 160 cag cta ctg agc atg cac gga agt gtt cct tcc gcg tggtca gcc tac 528 Gln Leu Leu Ser Met His Gly Ser Val Pro Ser Ala Trp SerAla Tyr 165 170 175 gtc acg ggg cgt gat tac agt cag cca act cag tac tacacg gaa gag 576 Val Thr Gly Arg Asp Tyr Ser Gln Pro Thr Gln Tyr Tyr ThrGlu Glu 180 185 190 gta gct gat tgg agg atg ctt tta cga gag gat gac atggca tct tcc 624 Val Ala Asp Trp Arg Met Leu Leu Arg Glu Asp Asp Met AlaSer Ser 195 200 205 tat ttg ctg ttg gtg gtg aca gag ggc aat gcc gcg gagttg tgg act 672 Tyr Leu Leu Leu Val Val Thr Glu Gly Asn Ala Ala Glu LeuTrp Thr 210 215 220 tat gac cct tat tat act aaa aca ata ggg atg gaa cacggg tat tcg 720 Tyr Asp Pro Tyr Tyr Thr Lys Thr Ile Gly Met Glu His GlyTyr Ser 225 230 235 240 gtc aga tgg tat ttt att agg gat agg aat gtg ggcgag gct ccc att 768 Val Arg Trp Tyr Phe Ile Arg Asp Arg Asn Val Gly GluAla Pro Ile 245 250 255 gtt tta tat gct agg ggc ggg ggt gta tta aaa tttatt aga ctg tac 816 Val Leu Tyr Ala Arg Gly Gly Gly Val Leu Lys Phe IleArg Leu Tyr 260 265 270 aag ggg cgt ggc act ctg acg tca cta ggg gcg agggca atg acg aca 864 Lys Gly Arg Gly Thr Leu Thr Ser Leu Gly Ala Arg AlaMet Thr Thr 275 280 285 cag gaa gtg acg gag ttt acg tgt ttc cgg act cacacc tat tac ttt 912 Gln Glu Val Thr Glu Phe Thr Cys Phe Arg Thr His ThrTyr Tyr Phe 290 295 300 acc gga act aag aag tac gat tgc cat cca ggc gggcac cgc ttt gat 960 Thr Gly Thr Lys Lys Tyr Asp Cys His Pro Gly Gly HisArg Phe Asp 305 310 315 320 gtc cct aga tgg cgc tct cat atc aat gtt tctgcg cac cat ctt cct 1008 Val Pro Arg Trp Arg Ser His Ile Asn Val Ser AlaHis His Leu Pro 325 330 335 gtc ccg ccc aaa tgt ggc tgt ttg aag ttc cccaaa ttg ttt aag gat 1056 Val Pro Pro Lys Cys Gly Cys Leu Lys Phe Pro LysLeu Phe Lys Asp 340 345 350 tat gtc ata ttt gat cac ccg aat gta gtg ggcagg gcc gga gaa tat 1104 Tyr Val Ile Phe Asp His Pro Asn Val Val Gly ArgAla Gly Glu Tyr 355 360 365 gtt agt tta ggg ccc tgg agt acc ggg tta caggcc gta gtg acc ttt 1152 Val Ser Leu Gly Pro Trp Ser Thr Gly Leu Gln AlaVal Val Thr Phe 370 375 380 aaa cct caa cct cga cgt cac cga gtg gtc ctggct acg tac tgg gat 1200 Lys Pro Gln Pro Arg Arg His Arg Val Val Leu AlaThr Tyr Trp Asp 385 390 395 400 gcc tgt tca aac acc aag agg cgt gtc ggcatt gac gtc aga acg gac 1248 Ala Cys Ser Asn Thr Lys Arg Arg Val Gly IleAsp Val Arg Thr Asp 405 410 415 cgg aag aat cac atg gtt tgg ctc aag gcggac aag cct gtg tcc aga 1296 Arg Lys Asn His Met Val Trp Leu Lys Ala AspLys Pro Val Ser Arg 420 425 430 gag atg tgg ttt gta tcg gaa gtg gac gtcgtt cga gtc tac gtc acg 1344 Glu Met Trp Phe Val Ser Glu Val Asp Val ValArg Val Tyr Val Thr 435 440 445 tgg ctc tcc ccc gaa taa 1362 Trp Leu SerPro Glu 450 48 453 PRT CELO VIRUS Position34238..35599/note=ORF19 48 MetArg Gly Phe Val Pro Pro Thr Ser Ser Pro Asp Arg Gly Ser Lys 1 5 10 15Lys Val Gly Arg Ile Val Ala Leu Asp Pro Pro Leu Glu Ser Phe Gln 20 25 30Gly Tyr Arg Met Asp Leu His Thr Lys Gly Leu Asn Leu Leu Leu Ser 35 40 45Ser Gly Gly His Trp Ser Ala Asn Arg Asp Ala Asp Ser Val Ile Ser 50 55 60Arg Asp Asp Ala Asp Tyr Val Val Val Ile Ala Ser Ser Ile Gly Ser 65 70 7580 Tyr Gly Phe Asp Arg Pro Ile Gly Asp Glu Tyr Ile Arg Ser Asp Leu 85 9095 Thr Gly Gln Lys His Glu Ala Cys Glu Ser Arg Ala Trp Trp Lys Gly 100105 110 Gln Ile Cys Ala Trp Ser Tyr Ser Gly Arg Arg His Cys Glu Asp Val115 120 125 His Ile Pro Phe Asp Phe Leu Arg Ser Asp Gly Leu Cys Tyr HisIle 130 135 140 Met Ala Pro Leu Thr Phe Met Lys Ala Leu Asp Thr His GlnAla Asp 145 150 155 160 Gln Leu Leu Ser Met His Gly Ser Val Pro Ser AlaTrp Ser Ala Tyr 165 170 175 Val Thr Gly Arg Asp Tyr Ser Gln Pro Thr GlnTyr Tyr Thr Glu Glu 180 185 190 Val Ala Asp Trp Arg Met Leu Leu Arg GluAsp Asp Met Ala Ser Ser 195 200 205 Tyr Leu Leu Leu Val Val Thr Glu GlyAsn Ala Ala Glu Leu Trp Thr 210 215 220 Tyr Asp Pro Tyr Tyr Thr Lys ThrIle Gly Met Glu His Gly Tyr Ser 225 230 235 240 Val Arg Trp Tyr Phe IleArg Asp Arg Asn Val Gly Glu Ala Pro Ile 245 250 255 Val Leu Tyr Ala ArgGly Gly Gly Val Leu Lys Phe Ile Arg Leu Tyr 260 265 270 Lys Gly Arg GlyThr Leu Thr Ser Leu Gly Ala Arg Ala Met Thr Thr 275 280 285 Gln Glu ValThr Glu Phe Thr Cys Phe Arg Thr His Thr Tyr Tyr Phe 290 295 300 Thr GlyThr Lys Lys Tyr Asp Cys His Pro Gly Gly His Arg Phe Asp 305 310 315 320Val Pro Arg Trp Arg Ser His Ile Asn Val Ser Ala His His Leu Pro 325 330335 Val Pro Pro Lys Cys Gly Cys Leu Lys Phe Pro Lys Leu Phe Lys Asp 340345 350 Tyr Val Ile Phe Asp His Pro Asn Val Val Gly Arg Ala Gly Glu Tyr355 360 365 Val Ser Leu Gly Pro Trp Ser Thr Gly Leu Gln Ala Val Val ThrPhe 370 375 380 Lys Pro Gln Pro Arg Arg His Arg Val Val Leu Ala Thr TyrTrp Asp 385 390 395 400 Ala Cys Ser Asn Thr Lys Arg Arg Val Gly Ile AspVal Arg Thr Asp 405 410 415 Arg Lys Asn His Met Val Trp Leu Lys Ala AspLys Pro Val Ser Arg 420 425 430 Glu Met Trp Phe Val Ser Glu Val Asp ValVal Arg Val Tyr Val Thr 435 440 445 Trp Leu Ser Pro Glu 450 49 816 DNACELO VIRUS CDS (1)..(816) 49 atg gag aga ctg aac gag tac cgc ata aat agagcc gtg gct agc ttg 48 Met Glu Arg Leu Asn Glu Tyr Arg Ile Asn Arg AlaVal Ala Ser Leu 1 5 10 15 cgg tgt ttc gat aat gat ctg atg agg cga ttgcat agt tct gtc acg 96 Arg Cys Phe Asp Asn Asp Leu Met Arg Arg Leu HisSer Ser Val Thr 20 25 30 gtg cta gtg acg gta cgc agc gca aag ttt gtg tgtttc aaa cgg cga 144 Val Leu Val Thr Val Arg Ser Ala Lys Phe Val Cys PheLys Arg Arg 35 40 45 gac tac gta ctc atg aat tgc ata gtc cgg att gtg agtgcc ctt cac 192 Asp Tyr Val Leu Met Asn Cys Ile Val Arg Ile Val Ser AlaLeu His 50 55 60 ctg aac cgg gca gag aag acc gcc ctg ctg cac tac ctc tcacgt agg 240 Leu Asn Arg Ala Glu Lys Thr Ala Leu Leu His Tyr Leu Ser ArgArg 65 70 75 80 ttg ctt ttt att aca cct ggg atg aag tac gac ttg gaa ccgtgg atg 288 Leu Leu Phe Ile Thr Pro Gly Met Lys Tyr Asp Leu Glu Pro TrpMet 85 90 95 ctt gct cgc agg aag aca gat ttt aag ttt ttc acc aca ggc tttctg 336 Leu Ala Arg Arg Lys Thr Asp Phe Lys Phe Phe Thr Thr Gly Phe Leu100 105 110 att gcg gag aag ata tcc gta aag atg gct ctc cgc tcg atg agcttt 384 Ile Ala Glu Lys Ile Ser Val Lys Met Ala Leu Arg Ser Met Ser Phe115 120 125 gag gtg tcc ttt tcg caa gtg cct tcg tct gtt cct ttt gtg cggtct 432 Glu Val Ser Phe Ser Gln Val Pro Ser Ser Val Pro Phe Val Arg Ser130 135 140 ccg gtt gtt ctc atg aat gcg tgt cgc gtg acc gtg acg gcc accatc 480 Pro Val Val Leu Met Asn Ala Cys Arg Val Thr Val Thr Ala Thr Ile145 150 155 160 atg gtg gaa act att tct cgc agc agc gcc gtg acc caa cccgtc tgc 528 Met Val Glu Thr Ile Ser Arg Ser Ser Ala Val Thr Gln Pro ValCys 165 170 175 ctg aga agc atg ctc cgc gtg atg gtg tcg ccg gaa ctg tggccg atc 576 Leu Arg Ser Met Leu Arg Val Met Val Ser Pro Glu Leu Trp ProIle 180 185 190 gtg tcg cag gga ctg tgt tac ttc ccc ggt tac cgt cgg ttgtcc tac 624 Val Ser Gln Gly Leu Cys Tyr Phe Pro Gly Tyr Arg Arg Leu SerTyr 195 200 205 gct aac gtc gaa gag tgg gta ttt cat gtg cac ggg aag tacggg gag 672 Ala Asn Val Glu Glu Trp Val Phe His Val His Gly Lys Tyr GlyGlu 210 215 220 tct cat ccc gag tgt ttc gga cag tgc aaa cag tgt tcg acgcgg caa 720 Ser His Pro Glu Cys Phe Gly Gln Cys Lys Gln Cys Ser Thr ArgGln 225 230 235 240 cct ctc tct ctg ttc tgt tct gct cag ttg gct tat ctgcgc aat gtg 768 Pro Leu Ser Leu Phe Cys Ser Ala Gln Leu Ala Tyr Leu ArgAsn Val 245 250 255 ttt atg gaa cga cgc gcg aga gtc gct ggt gaa cgt ccgtat agc taa 816 Phe Met Glu Arg Arg Ala Arg Val Ala Gly Glu Arg Pro TyrSer 260 265 270 50 271 PRT CELO VIRUS Position32892..33707/note=ORF20 50Met Glu Arg Leu Asn Glu Tyr Arg Ile Asn Arg Ala Val Ala Ser Leu 1 5 1015 Arg Cys Phe Asp Asn Asp Leu Met Arg Arg Leu His Ser Ser Val Thr 20 2530 Val Leu Val Thr Val Arg Ser Ala Lys Phe Val Cys Phe Lys Arg Arg 35 4045 Asp Tyr Val Leu Met Asn Cys Ile Val Arg Ile Val Ser Ala Leu His 50 5560 Leu Asn Arg Ala Glu Lys Thr Ala Leu Leu His Tyr Leu Ser Arg Arg 65 7075 80 Leu Leu Phe Ile Thr Pro Gly Met Lys Tyr Asp Leu Glu Pro Trp Met 8590 95 Leu Ala Arg Arg Lys Thr Asp Phe Lys Phe Phe Thr Thr Gly Phe Leu100 105 110 Ile Ala Glu Lys Ile Ser Val Lys Met Ala Leu Arg Ser Met SerPhe 115 120 125 Glu Val Ser Phe Ser Gln Val Pro Ser Ser Val Pro Phe ValArg Ser 130 135 140 Pro Val Val Leu Met Asn Ala Cys Arg Val Thr Val ThrAla Thr Ile 145 150 155 160 Met Val Glu Thr Ile Ser Arg Ser Ser Ala ValThr Gln Pro Val Cys 165 170 175 Leu Arg Ser Met Leu Arg Val Met Val SerPro Glu Leu Trp Pro Ile 180 185 190 Val Ser Gln Gly Leu Cys Tyr Phe ProGly Tyr Arg Arg Leu Ser Tyr 195 200 205 Ala Asn Val Glu Glu Trp Val PheHis Val His Gly Lys Tyr Gly Glu 210 215 220 Ser His Pro Glu Cys Phe GlyGln Cys Lys Gln Cys Ser Thr Arg Gln 225 230 235 240 Pro Leu Ser Leu PheCys Ser Ala Gln Leu Ala Tyr Leu Arg Asn Val 245 250 255 Phe Met Glu ArgArg Ala Arg Val Ala Gly Glu Arg Pro Tyr Ser 260 265 270 51 324 DNA CELOVIRUS CDS (1)..(324) 51 atg tgc acg gga agt acg ggg agt ctc atc ccg agtgtt tcg gac agt 48 Met Cys Thr Gly Ser Thr Gly Ser Leu Ile Pro Ser ValSer Asp Ser 1 5 10 15 gca aac agt gtt cga cgc ggc aac ctc tct ctc tgttct gtt ctg ctc 96 Ala Asn Ser Val Arg Arg Gly Asn Leu Ser Leu Cys SerVal Leu Leu 20 25 30 agt tgg ctt atc tgc gca atg tgt tta tgg aac gac gcgcga gag tcg 144 Ser Trp Leu Ile Cys Ala Met Cys Leu Trp Asn Asp Ala ArgGlu Ser 35 40 45 ctg gtg aac gtc cgt ata gct aat tac gtg ttt gat ttt gcagtg ttg 192 Leu Val Asn Val Arg Ile Ala Asn Tyr Val Phe Asp Phe Ala ValLeu 50 55 60 tgg acg cta ttg gcg cga gtt ctt ggc cct cct ggt cgc cct gtccta 240 Trp Thr Leu Leu Ala Arg Val Leu Gly Pro Pro Gly Arg Pro Val Leu65 70 75 80 cag cag cat cat cct gtg cag ctt cct gtt cct aca gaa cca tctgtc 288 Gln Gln His His Pro Val Gln Leu Pro Val Pro Thr Glu Pro Ser Val85 90 95 ttc gtt aaa ctt tgt aat cag cgt gtt cgt ttg tag 324 Phe Val LysLeu Cys Asn Gln Arg Val Arg Leu 100 105 52 107 PRT CELO VIRUSPosition32735..33058/note=ORF21 52 Met Cys Thr Gly Ser Thr Gly Ser LeuIle Pro Ser Val Ser Asp Ser 1 5 10 15 Ala Asn Ser Val Arg Arg Gly AsnLeu Ser Leu Cys Ser Val Leu Leu 20 25 30 Ser Trp Leu Ile Cys Ala Met CysLeu Trp Asn Asp Ala Arg Glu Ser 35 40 45 Leu Val Asn Val Arg Ile Ala AsnTyr Val Phe Asp Phe Ala Val Leu 50 55 60 Trp Thr Leu Leu Ala Arg Val LeuGly Pro Pro Gly Arg Pro Val Leu 65 70 75 80 Gln Gln His His Pro Val GlnLeu Pro Val Pro Thr Glu Pro Ser Val 85 90 95 Phe Val Lys Leu Cys Asn GlnArg Val Arg Leu 100 105 53 618 DNA CELO VIRUS CDS (1)..(618) 53 atg aacgac gag cag atc ctg gag atg gtg ctg cag cac cag cag cgc 48 Met Asn AspGlu Gln Ile Leu Glu Met Val Leu Gln His Gln Gln Arg 1 5 10 15 cgc caacag gaa gcg gag cgc gag gag gaa gtt ggg gat gac atg gaa 96 Arg Gln GlnGlu Ala Glu Arg Glu Glu Glu Val Gly Asp Asp Met Glu 20 25 30 gac gac gaagat gat gac ggt ctt cag atg ccg acg ccg ctt cat gcc 144 Asp Asp Glu AspAsp Asp Gly Leu Gln Met Pro Thr Pro Leu His Ala 35 40 45 tat cag cta ctgtgt tac gat tct ttc gaa ctt cat ttc ggg gga tgc 192 Tyr Gln Leu Leu CysTyr Asp Ser Phe Glu Leu His Phe Gly Gly Cys 50 55 60 gct tgc cac ggg ttacct ttg cat cgt atg ggg tta tcg gct tgc cac 240 Ala Cys His Gly Leu ProLeu His Arg Met Gly Leu Ser Ala Cys His 65 70 75 80 ctg gct cct tcc gatttg gcc act tat gtt tgg gcc agg ttg gag gat 288 Leu Ala Pro Ser Asp LeuAla Thr Tyr Val Trp Ala Arg Leu Glu Asp 85 90 95 gac ttg aat gtg gca ggggtg tac ttc gtg gct atg tgg gcg tca ccg 336 Asp Leu Asn Val Ala Gly ValTyr Phe Val Ala Met Trp Ala Ser Pro 100 105 110 ggg ttt agc gat ttc tctcca gta ttt atg cag cga ccg atc ggg aac 384 Gly Phe Ser Asp Phe Ser ProVal Phe Met Gln Arg Pro Ile Gly Asn 115 120 125 gtg tgc ggg atg tta attcac gtg gac ctg cac agc agg cta cca ttc 432 Val Cys Gly Met Leu Ile HisVal Asp Leu His Ser Arg Leu Pro Phe 130 135 140 cta att gcg gtg tcg cgcttg ggg gag gcg ggt ggc agc ccc tgt ctg 480 Leu Ile Ala Val Ser Arg LeuGly Glu Ala Gly Gly Ser Pro Cys Leu 145 150 155 160 tat atg agg aaa attgat gtt gat ttg gac acg cag cgc gta cat ttt 528 Tyr Met Arg Lys Ile AspVal Asp Leu Asp Thr Gln Arg Val His Phe 165 170 175 tat aca gaa gat tggttc agt gag ttt gcg aat ctg ctg tat tac tgg 576 Tyr Thr Glu Asp Trp PheSer Glu Phe Ala Asn Leu Leu Tyr Tyr Trp 180 185 190 caa atg agc gaa tggaaa cat tta gcg gag cgt atg caa taa 618 Gln Met Ser Glu Trp Lys His LeuAla Glu Arg Met Gln 195 200 205 54 205 PRT CELO VIRUSPosition31812..32429/note=ORF22 54 Met Asn Asp Glu Gln Ile Leu Glu MetVal Leu Gln His Gln Gln Arg 1 5 10 15 Arg Gln Gln Glu Ala Glu Arg GluGlu Glu Val Gly Asp Asp Met Glu 20 25 30 Asp Asp Glu Asp Asp Asp Gly LeuGln Met Pro Thr Pro Leu His Ala 35 40 45 Tyr Gln Leu Leu Cys Tyr Asp SerPhe Glu Leu His Phe Gly Gly Cys 50 55 60 Ala Cys His Gly Leu Pro Leu HisArg Met Gly Leu Ser Ala Cys His 65 70 75 80 Leu Ala Pro Ser Asp Leu AlaThr Tyr Val Trp Ala Arg Leu Glu Asp 85 90 95 Asp Leu Asn Val Ala Gly ValTyr Phe Val Ala Met Trp Ala Ser Pro 100 105 110 Gly Phe Ser Asp Phe SerPro Val Phe Met Gln Arg Pro Ile Gly Asn 115 120 125 Val Cys Gly Met LeuIle His Val Asp Leu His Ser Arg Leu Pro Phe 130 135 140 Leu Ile Ala ValSer Arg Leu Gly Glu Ala Gly Gly Ser Pro Cys Leu 145 150 155 160 Tyr MetArg Lys Ile Asp Val Asp Leu Asp Thr Gln Arg Val His Phe 165 170 175 TyrThr Glu Asp Trp Phe Ser Glu Phe Ala Asn Leu Leu Tyr Tyr Trp 180 185 190Gln Met Ser Glu Trp Lys His Leu Ala Glu Arg Met Gln 195 200 205

What is claimed is:
 1. A fowl adenovirus type 1 (CELO) virus DNAcomprising the left and right inverted terminal repeats and thepackaging signal of the CELO virus genome, wherein said CELO virus DNAcontains a deletion of all or part of, an insertion in, or a mutationin, one or more non-essential regions selected from the group consistingof: (a) nucleotides from about 794 to about 1,330 of SEQ ID NO:1; and(b) nucleotides from about 28,114 to about 30,495 of SEQ ID NO:1.
 2. TheCELO virus DNA of claim 1, wherein said deletion, insertion or mutationoccurs within nucleotides from about 794 to about 1,330 of SEQ ID NO:1.3. The CELO virus DNA of claim 2, wherein said CELO virus DNA contains adeletion of nucleotides from about 794 to about 1,330 of SEQ ID NO:1. 4.A fowl adenovirus type 1 (CELO) virus DNA comprising the left and rightinverted terminal repeats and the packaging signal of the CELO virusgenome, wherein said CELO virus DNA contains a deletion of part of, aninsertion in, or a mutation in, a non-essential region consisting ofnucleotides from about 31,800 to about 43,734 of SEQ ID NO:1, andwherein said CELO virus DNA yields CELO virus particles in suitablecells with or without complementation.
 5. The CELO virus DNA of claim 4,wherein said CELO virus DNA further contains a deletion, insertion ormutation within nucleotides from about 794 to about 1,330 of SEQ IDNO:1.
 6. The CELO virus DNA of claim 1, wherein said deletion, insertionor mutation occurs within nucleotides from about 28,114 to about 30,495of SEQ ID NO:1.
 7. The CELO virus DNA of claim 6, wherein said CELOvirus DNA contains a deletion of nucleotides from about 28,114 to about30,495 of SEQ ID NO:1.
 8. The CELO virus DNA of claim 5, wherein saidCELO virus DNA contains a deletion of nucleotides from about 794 toabout 1,330 of SEQ ID NO:1.
 9. The CELO virus DNA of claim 4, whereinsaid CELO virus DNA further contains a deletion, insertion or mutationwithin nucleotides from about 28,114 to about 30,495 of SEQ ID NO:1. 10.The CELO virus DNA of claim 1, wherein said deletion, insertion ormutation occurs within nucleotides from about 794 to about 1,330 andnucleotides from about 28,114 to about 30,495 of SEQ ID NO:1.
 11. TheCELO virus DNA of claim 10, wherein said CELO virus DNA contains adeletion of nucleotides from about 794 to about 1,330 and nucleotidesfrom about 28,114 to about 30,495 of SEQ ID NO:1.
 12. The CELO virus DNAof claim 9, wherein said CELO virus DNA contains a deletion ofnucleotides from about 28,114 to about 30,495 of SEQ ID NO:1.
 13. TheCELO virus DNA of claim 4, wherein CELO virus DNA further contains adeletion, insertion or mutation within nucleotides from about 794 toabout 1,330 and nucleotides from about 28,114 to about 30,495 of SEQ IDNO:1.
 14. The CELO virus DNA of claim 13, wherein said CELO virus DNAcontains a deletion of nucleotides from about 794 to about 1,330 andnucleotides from about 28,114 to about 30,495 of SEQ ID NO:1.
 15. TheCELO virus DNA of claim 4, wherein said CELO virus genome comprisesnucleotides 1 to 43,804 in SEQ ID NO:1.
 16. The CELO virus DNA of claim4, wherein said CELO virus DNA is contained on a plasmid whichreplicates in bacteria or yeast and which yields virus particles afterbeing introduced into cells.
 17. The CELO virus DNA of claim 1, whereinsaid CELO virus genome comprises nucleotides 1 to 43,804 in SEQ ID NO:1.18. The CELO virus DNA of claim 1, wherein said CELO virus DNA iscontained on a plasmid which replicates in bacteria or yeast and whichyields virus particles after being introduced into cells.
 19. The CELOvirus DNA of claim 18, wherein said CELO virus DNA contains a deletionof a gene which is necessary for the formation of mature virusparticles, and wherein said CELO virus DNA, after being introduced intocells together with a plasmid which complements said deleted gene,yields mature virus particles.
 20. The CELO virus DNA of claim 1,wherein said CELO virus DNA contains foreign DNA.
 21. The CELO virus DNAof claim 20, wherein said foreign DNA encodes a protein.
 22. The CELOvirus DNA of claim 20, wherein said foreign DNA is inserted in a deletedsection.
 23. The CELO virus DNA of claim 19, wherein said CELO virus DNAcontains foreign DNA.
 24. The CELO virus DNA of claim 23, wherein saidforeign DNA encodes a protein.
 25. The CELO virus DNA of claim 23,wherein said foreign DNA is inserted in a deleted section.
 26. The CELOvirus DNA of claim 21, wherein said foreign DNA codes for atherapeutically active protein.
 27. The CELO virus DNA of claim 26,wherein said foreign DNA codes for an immunostimulatory protein.
 28. TheCELO virus DNA of claim 27, wherein said foreign DNA codes for acytokine.
 29. The CELO virus DNA of claim 26, wherein said foreign DNAcodes for a protein selected from the group consisting of IL-1, IL-2,IL-6, IL-12, GM-CSF, an interferon, IκB, a glucocorticoid receptor, acatalase, manganese superoxide dismutase, glutathione peroxidase, LIP,LAP, ADF, Bcl-2, adenovirus E1B19K, Mcl-2, BAX, IRF-2, ICE protease,cJun, TAM-67, adenovirus E1A, p53, factor VIII, factor IX,erythropoietin, cystic fibrosis transmembrane regulator, dystrophin,globin, the LDL receptor and β-glucuronidase.
 30. The CELO virus DNA ofclaim 20, wherein said foreign DNA codes for a tumor antigen or animmunogenic fragment thereof.
 31. The CELO virus DNA of claim 20,wherein said foreign DNA codes for an antigen from a human pathogen. 32.The CELO virus DNA of claim 20, wherein said foreign DNA codes for anantigen from an animal pathogen.
 33. The CELO virus DNA of claim 32,wherein said foreign DNA codes for an antigen from a bird pathogen. 34.The CELO virus DNA of claim 20, wherein said foreign DNA codes for aligand for mammalian cells.
 35. The CELO virus DNA of claim 16, whereinsaid CELO virus DNA contains a deletion of a gene which is necessary forthe formation of mature virus particles, and wherein said CELO virusDNA, after being introduced into cells together with a plasmid whichcomplements said deleted gene, yields mature virus particles.
 36. TheCELO virus DNA of claim 20, wherein said CELO virus DNA contains saidforeign DNA on a section comprising nucleotides from about 28,114 toabout 30,495 of SEQ ID NO:1, which contains the fibre 1 gene.
 37. TheCELO virus DNA of claim 20, wherein said CELO virus DNA contains saidforeign DNA in the region of the reading frame at nucleotide 794 of SEQID NO:1 which codes for dUTPase.
 38. The CELO virus DNA of claim 1,wherein said left terminal repeat comprises nucleotides 1 to 68 in SEQID NO:1, said packaging signal comprises nucleotides 70 to 200 in SEQ IDNO:1, and said right terminal repeat comprises nucleotides 43,734 to43,804 in SEQ ID NO:1.
 39. The CELO virus DNA of claim 20, wherein saidforeign DNA is operably associated with a regulatory sequence.
 40. TheCELO virus DNA of claim 23, wherein said foreign DNA is operablyassociated with a regulatory sequence.
 41. The CELO virus DNA of claim39, wherein said regulatory sequence is selected from the groupconsisting of promoters and enhancers.
 42. The CELO virus DNA of claim41, wherein said promoter is selected from the group consisting of theCMV immediate early promoter, the Rous Sarcoma Virus LTR, the adenovirusmajor late promoter and the CELO virus major late promoter.
 43. A hostcell comprising the CELO virus DNA of claim
 1. 44. A host cellcomprising the CELO virus DNA of claim
 20. 45. A host cell comprisingthe CELO virus DNA of claim
 23. 46. A host cell comprising the CELOvirus DNA of claim
 39. 47. A host cell comprising the CELO virus DNA ofclaim
 40. 48. A method for producing a protein comprising culturing thehost cell of claim 44 under conditions such that said protein isexpressed, and recovering said protein.
 49. A method for producing aprotein comprising culturing the host cell of claim 45 under conditionssuch that said protein is expressed, and recovering said protein.
 50. Afowl adenovirus type 1 (CELO) virus DNA comprising the left and rightinverted terminal repeats and the packaging signal of the CELO virusgenome, wherein said CELO virus DNA contains a deletion of nucleotideswithin the region from about 201 to about 5,000 of SEQ ID NO:1, andwherein said CELO virus DNA yields CELO virus particles in suitablecells with or without complementation.
 51. The CELO virus DNA of claim50, wherein said CELO virus genome comprises nucleotides 1 to 43,804 inSEQ ID NO:1.
 52. The CELO virus DNA of claim 50, wherein said CELO virusDNA is contained on a plasmid which replicates in bacteria or yeast andwhich yields virus particles after being introduced into cells.
 53. TheCELO virus DNA of claim 52, wherein said CELO virus DNA contains adeletion of a gene which is necessary for the formation of mature virusparticles, and wherein said CELO virus DNA, after being introduced intocells together with a plasmid which complements said deleted gene,yields mature virus particles.
 54. The CELO virus DNA of claim 50,wherein said CELO virus DNA contains foreign DNA.
 55. The CELO virus DNAof claim 54, wherein said foreign DNA encodes a protein.
 56. The CELOvirus DNA of claim 54, wherein said foreign DNA is inserted in thedeleted section.
 57. The CELO virus DNA of claim 53, wherein said CELOvirus DNA contains foreign DNA.
 58. The CELO virus DNA of claim 57,wherein said foreign DNA encodes a protein.
 59. The CELO virus DNA ofclaim 57, wherein said foreign DNA is inserted in the deleted section.60. The CELO virus DNA of claim 55, wherein said foreign DNA codes for atherapeutically active protein.
 61. The CELO virus DNA of claim 60,wherein said foreign DNA codes for an immunostimulatory protein.
 62. TheCELO virus DNA of claim 61, wherein said foreign DNA codes for acytokine.
 63. The CELO virus DNA of claim 60, wherein said foreign DNAcodes for a protein selected from the group consisting of IL-1, IL-2,IL-6, IL-12, GM-CSF, an interferon, IκB, a glucocorticoid receptor, acatalase, manganese superoxide dismutase, glutathione peroxidase, LIP,LAP, ADF, Bcl-2, adenovirus E1B19K, Mcl-2, BAX, IRF-2, ICE protease,cjun, TAM-67, adenovirus E1A, p53, factor VIII, factor IX,erythropoietin, cystic fibrosis transmembrane regulator, dystrophin,globin, the LDL receptor and β-glucuronidase.
 64. The CELO virus DNA ofclaim 54, wherein said foreign DNA codes for a tumor antigen or animmunogenic fragment thereof.
 65. The CELO virus DNA of claim 54,wherein said foreign DNA codes for an antigen from a human pathogen. 66.The CELO virus DNA of claim 54, wherein said foreign DNA codes for anantigen from an animal pathogen.
 67. The CELO virus DNA of claim 66,wherein said foreign DNA codes for an antigen from a bird pathogen. 68.The CELO virus DNA of claim 54, wherein said foreign DNA codes for aligand for mammalian cells.
 69. The CELO virus DNA of claim 50, whereinsaid left terminal repeat comprises nucleotides 1 to 68 in SEQ ID NO:1,said packaging signal comprises nucleotides 70 to 200 in SEQ ID NO:1,and said right terminal repeat comprises nucleotides 43,734 to 43,804 inSEQ ID NO:1.
 70. The CELO virus DNA of claim 54, wherein said foreignDNA is operably associated with a regulatory sequence.
 71. The CELOvirus DNA of claim 57, wherein said foreign DNA is operably associatedwith a regulatory sequence.
 72. The CELO virus DNA of claim 70, whereinsaid regulatory sequence is selected from the group consisting ofpromoters and enhancers.
 73. The CELO virus DNA of claim 72, whereinsaid promoter is selected from the group consisting of the CMV immediateearly promoter, the Rous Sarcoma Virus LTR, the adenovirus major latepromoter and the CELO virus major late promoter.
 74. A host cellcomprising the CELO virus DNA of claim
 50. 75. A host cell comprisingthe CELO virus DNA of claim
 54. 76. A host cell comprising the CELOvirus DNA of claim
 57. 77. A host cell comprising the CELO virus DNA ofclaim
 70. 78. A host cell comprising the CELO virus DNA of claim
 71. 79.A method for producing of a protein comprising culturing the host cellof claim 54 under conditions such that said protein is expressed, andrecovering said protein.
 80. A method for producing of a proteincomprising culturing the host cell of claim 57 under conditions suchthat said protein is expressed, and recovering said protein.
 81. Processfor preparing recombinant CELO virus DNA according to claim 1,characterized in that the CELO virus genome or sections thereof arecontained on a plasmid and are genetically manipulated.
 82. Processaccording to claim 81, characterized in that the CELO virus genome orsections thereof contained on a plasmid are manipulated in a regionwhich is different from the left and right inverted terminal repeat andfrom the packaging signal.
 83. Process according to claim 81,characterized in that insertions, insertions and deletions, or deletionsare carried out.
 84. Process according to claim 82, characterized inthat insertions, insertions and deletions, or deletions are carried out.85. Process according to claim 83, characterized in that a foreign geneis inserted in a naturally occurring or artificially introducedrestriction cutting site on a section of the CELO virus DNA whichcontains a sequence which is not necessary for the replication of thevirus in the host cell or which can be complemented.
 86. Processaccording to claim 85, characterized in that in addition to theinsertion, a deletion is carried out in another region of the CELO virusDNA which contains a sequence which is not necessary for the replicationof the virus in the host cell or which can be complemented.
 87. Processaccording to claim 81, characterized in that the manipulation is carriedout by recombination.
 88. Process according to claim 82, characterizedin that the manipulation is carried out by recombination.
 89. Processaccording to claim 87, characterized in that DNA molecules obtained bypolymerase chain reaction are recombined.
 90. Process according to claim87, characterized in that DNA molecules obtained by ligation arerecombined.
 91. Process according to claim 87, characterized in that DNAmolecules obtained by cloning in bacteria are recombined.
 92. Processfor preparing recombinant CELO virus DNA according to claim 91,comprising: (a) cloning a CELO virus DNA fragment containing tworestriction sites into a bacterial plasmid; (b) inserting foreign DNAbetween these restriction sites which occur only once on the plasmid;(c) excising the fragment containing the foreign DNA from the plasmidand mixing said fragment with a plasmid which contains the complete CELOvirus DNA and which has been cut at a restriction cutting site whichoccurs only once; (d) transforming the bacteria with this mixture of DNAmolecules and growing the bacteria; and (e) obtaining a plasmid byrecombination of the DNA molecules which contains the entire CELO virusDNA with the foreign DNA as an insert.
 93. Process according to claim85, characterized in that a reporter gene is inserted as the foreignDNA.
 94. Process according to claim 87, characterized in that a reportergene is inserted as the foreign DNA.
 95. Process according to claim 93,characterized in that the reporter gene has a restriction cutting siteinto which foreign DNA which codes for a therapeutically active proteinis inserted in an additional step.
 96. Process according to claim 93,characterized in that the reporter gene has a restriction cutting siteinto which foreign DNA which codes for a tumor antigen or a fragmentthereof is inserted in an additional step.
 97. Process according toclaim 93, characterized in that the reporter gene has a restrictioncutting site into which foreign DNA which codes for an antigen derivedfrom a human pathogen is inserted in an additional step.
 98. Processaccording to claim 93, characterized in that the reporter gene has arestriction cutting site into which foreign DNA which codes for anantigen derived from an animal pathogen is inserted in an additionalstep.
 99. Process according to claim 93, characterized in that thereporter gene has a restriction cutting site into which foreign DNAwhich codes for a ligand for mammalian cells is inserted in anadditional step.
 100. Process according to claim 94, characterized inthat the reporter gene has a restriction cutting site into which foreignDNA which codes for a therapeutically active protein is inserted in anadditional step.
 101. Process according to claim 94, characterized inthat the reporter gene has a restriction cutting site into which foreignDNA which codes for a tumor antigen or a fragment thereof is inserted inan additional step.
 102. Process according to claim 94, characterized inthat the reporter gene has a restriction cutting site into which foreignDNA which codes for an antigen derived from a human pathogen is insertedin an additional step.
 103. Process according to claim 94, characterizedin that the reporter gene has a restriction cutting site into whichforeign DNA which codes for an antigen derived from an animal pathogenis inserted in an additional step.
 104. Process according to claim 94,characterized in that the reporter gene has a restriction cutting siteinto which foreign DNA which codes for a ligand for mammalian cell isinserted in an additional step.
 105. Process for preparing CELO viruswhich comprises: (a) transforming avian cells with a plasmid containingCELO virus DNA of claim 1, thereby obtaining transformed cells; (b)cultivating said transformed cells (a), thereby obtaining a cellculture; and (c) harvesting said cell culture (b), thereby preparingCELO virus.
 106. Process according to claim 105, characterized in thatthe CELO virus DNA lacks sequences which are necessary for the formationof mature virus particles, the process which further comprisescomplementing said sequences.
 107. Process according to claim 106,characterized in that the avian cells used are helper cells whichcomplement said sequences which are necessary for the formation ofmature virus particles.
 108. Process according to claim 106,characterized in that the avian cells are also transformed with aplasmid which complements said sequences necessary for the formation ofmature virus particles.
 109. Process according to claim 106,characterized in that the avian cells are also infected with a helpervirus which complements said sequences necessary for the formation ofmature virus particles.
 110. The CELO virus DNA of claim 4, wherein saidCELO virus DNA contains foreign DNA.
 111. The CELO virus DNA of claim110, wherein said foreign DNA encodes a protein.
 112. The CELO virus DNAof claim 110, wherein said foreign DNA is inserted in a deleted section.113. The CELO virus DNA of claim 35, wherein said CELO virus DNAcontains foreign DNA.
 114. The CELO virus DNA of claim 113, wherein saidforeign DNA encodes a protein.
 115. The CELO virus DNA of claim 113,wherein said foreign DNA is inserted in a deleted section.
 116. The CELOvirus DNA of claim 111, wherein said foreign DNA codes for atherapeutically active protein.
 117. The CELO virus DNA of claim 116,wherein said foreign DNA codes for an immunostimulatory protein. 118.The CELO virus DNA of claim 117, wherein said foreign DNA codes for acytokine.
 119. The CELO virus DNA of claim 116, wherein said foreign DNAcodes for a protein selected from the group consisting of IL-1, IL-2,IL-6, IL-12, GM-CSF, an interferon, IκB, a glucocorticoid receptor, acatalase, manganese superoxide dismutase, glutathione peroxidase, LIP,LAP, ADF, Bcl-2, adenovirus E1B19K, Mcl-2, BAX, IRF-2, ICE protease,cjun, TAM-67, adenovirus E1A, p53, factor VIII, factor IX,erythropoietin, cystic fibrosis transmembrane regulator, dystrophin,globin, the LDL receptor and β-glucuronidase.
 120. The CELO virus DNA ofclaim 110, wherein said foreign DNA codes for a tumor antigen or animmunogenic fragment thereof.
 121. The CELO virus DNA of claim 110,wherein said foreign DNA codes for an antigen from a human pathogen.122. The CELO virus DNA of claim 110, wherein said foreign DNA codes foran antigen from an animal pathogen.
 123. The CELO virus DNA of claim122, wherein said foreign DNA codes for an antigen from a bird pathogen.124. The CELO virus DNA of claim 110, wherein said foreign DNA codes fora ligand for mammalian cells.
 125. The CELO virus DNA of claim 110,wherein said CELO virus DNA contains said foreign DNA at about the FseIcutting site which is located at position 35,693 of SEQ ID NO:1. 126.The CELO virus DNA of claim 4, wherein said left terminal repeatcomprises nucleotides 1 to 68 in SEQ ID NO:1, said packaging signalcomprises nucleotides 70 to 200 in SEQ ID NO:1, and said right terminalrepeat comprises nucleotides 43,734 to 43,804 in SEQ ID NO:1.
 127. TheCELO virus DNA of claim 110, wherein said foreign DNA is operablyassociated with a regulatory sequence.
 128. The CELO virus DNA of claim113, wherein said foreign DNA is operably associated with a regulatorysequence.
 129. The CELO virus DNA of claim 127, wherein said regulatorysequence is selected from the group consisting of promoters andenhancers.
 130. The CELO virus DNA of claim 129, wherein said promoteris selected from the group consisting of the CMV immediate earlypromoter, the Rous Sarcoma Virus LTR, the adenovirus major late promoterand the CELO virus major late promoter.
 131. A host cell comprising theCELO virus DNA of claim
 4. 132. A host cell comprising the CELO virusDNA of claim
 110. 133. A host cell comprising the CELO virus DNA ofclaim
 113. 134. A host cell comprising the CELO virus DNA of claim 127.135. A host cell comprising the CELO virus DNA of claim
 128. 136. Amethod for producing a protein comprising culturing the host cell ofclaim 132 under conditions such that said protein is expressed, andrecovering said protein.
 137. A method for producing a proteincomprising culturing the host cell of claim 133 under conditions suchthat said protein is expressed, and recovering said protein.
 138. Aprocess for preparing recombinant CELO virus DNA according to claim 4,characterized in that the CELO virus genome or sections thereof arecontained on a plasmid and are genetically manipulated.
 139. The processaccording to claim 138, characterized in that the CELO virus genome orsections thereof contained on a plasmid are manipulated in a regionwhich is different from the left and right inverted terminal repeat andfrom the packaging signal.
 140. The process according to claim 138,characterized in that insertions, insertions and deletions, or deletionsare carried out.
 141. The process according to claim 139, characterizedin that insertions, insertions and deletions, or deletions are carriedout.
 142. The process according to claim 140, characterized in that aforeign gene is inserted in a naturally occurring or artificiallyintroduced restriction cutting site on a section of the CELO virus DNAwhich contains a sequence which is not necessary for the replication ofthe virus in the host cell or which can be complemented.
 143. Theprocess according to claim 142, characterized in that in addition to theinsertion, a deletion is carried out in another region of the CELO virusDNA which contains a sequence which is not necessary for the replicationof the virus in the host cell or which can be complemented.
 144. Theprocess according to claim 138, characterized in that the manipulationis carried out by recombination.
 145. The process according to claim139, characterized in that the manipulation is carried out byrecombination.
 146. The process according to claim 144, characterized inthat DNA molecules obtained by polymerase chain reaction are recombined.147. The process according to claim 144, characterized in that DNAmolecules obtained by ligation are recombined.
 148. The processaccording to claim 144, characterized in that DNA molecules obtained bycloning in bacteria are recombined.
 149. The process for preparingrecombinant CELO virus DNA according to claim 148, comprising: (a)cloning a CELO virus DNA fragment containing two restriction sites intoa bacterial plasmid; (b) inserting foreign DNA between these restrictionsites which occur only once on the plasmid; (c) excising the fragmentcontaining the foreign DNA from the plasmid and mixing said fragmentwith a plasmid which contains the complete CELO virus DNA and which hasbeen cut at a restriction cutting site which occurs only once; (d)transforming the bacteria with this mixture of DNA molecules and growingthe bacteria; and (e) obtaining a plasmid by recombination of the DNAmolecules which contains the entire CELO virus DNA with the foreign DNAas an insert.
 150. The process according to claim 142, characterized inthat a reporter gene is inserted as the foreign DNA.
 151. The processaccording to claim 144, characterized in that a reporter gene isinserted as the foreign DNA.
 152. The process according to claim 150,characterized in that the reporter gene has a restriction cutting siteinto which foreign DNA which codes for a therapeutically active proteinis inserted in an additional step.
 153. The process according to claim150, characterized in that the reporter gene has a restriction cuttingsite into which foreign DNA which codes for a tumor antigen or afragment thereof is inserted in an additional step.
 154. The processaccording to claim 150, characterized in that the reporter gene has arestriction cutting site into which foreign DNA which codes for anantigen derived from a human pathogen is inserted in an additional step.155. The process according to claim 150, characterized in that thereporter gene has a restriction cutting site into which foreign DNAwhich codes for an antigen derived from an animal pathogen is insertedin an additional step.
 156. The process according to claim 150,characterized in that the reporter gene has a restriction cutting siteinto which foreign DNA which codes for a ligand for mammalian cells isinserted in an additional step.
 157. The process according to claim 151,characterized in that the reporter gene has a restriction cutting siteinto which foreign DNA which codes for a therapeutically active proteinis inserted in an additional step.
 158. The process according to claim151, characterized in that the reporter gene has a restriction cuttingsite into which foreign DNA which codes for a tumor antigen or afragment thereof is inserted in an additional step.
 159. The processaccording to claim 151, characterized in that the reporter gene has arestriction cutting site into which foreign DNA which codes for anantigen derived from a human pathogen is inserted in an additional step.160. The process according to claim 151, characterized in that thereporter gene has a restriction cutting site into which foreign DNAwhich codes for an antigen derived from an animal pathogen is insertedin an additional step.
 161. The process according to claim 151,characterized in that the reporter gene has a restriction cutting siteinto which foreign DNA which codes for a ligand for mammalian cells isinserted in an additional step.
 162. A process for preparing CELO viruswhich comprises: (a) transforming avian cells with a plasmid containingCELO virus DNA of claim 4, thereby obtaining transformed cells; (b)cultivating said transformed cells (a), thereby obtaining a cellculture; and (c) harvesting said cell culture (b), thereby preparingCELO virus.
 163. The process according to claim 162, characterized inthat the CELO virus DNA lacks sequences which are necessary for theformation of mature virus particles and complementing said sequences.164. The process according to claim 163, characterized in that the aviancells used are helper cells which complement said sequences which arenecessary for the formation of mature virus particles.
 165. The processaccording to claim 163, characterized in that the avian cells are alsotransformed with a plasmid which complements said sequences necessaryfor the formation of mature virus particles.
 166. The process accordingto claim 163, characterized in that the avian cells are also infectedwith a helper virus which complements said sequences necessary for theformation of mature virus particles.